EP3401400 - METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION [Right-click to bookmark this link] | Status | The patent has been granted Status updated on 01.03.2019 Database last updated on 23.04.2024 | |
Former | Grant of patent is intended Status updated on 20.02.2019 | ||
Former | Request for examination was made Status updated on 12.02.2019 | ||
Former | Grant of patent is intended Status updated on 04.02.2019 | ||
Former | Request for examination was made Status updated on 23.11.2018 | ||
Former | The application has been published Status updated on 12.10.2018 | Most recent event Tooltip | 13.07.2023 | New entry: Date of oral proceedings | Applicant(s) | For all designated states The Regents of the University of California 1111 Franklin Street, 12th Floor Oakland, CA 94607 / US | For all designated states University of Vienna Universitätsring 1 1010 Vienna / AT | For all designated states Charpentier, Emmanuelle Department Of Regulation in Infection Biology Max Planck Institute for Infection Biology Charitéplatz 1 10117 Berlin / DE | [2018/46] | Inventor(s) | 01 /
CHARPENTIER, Emmanuelle Department Of Regulation in Infection Biology Max Planck Institute for Infection Biology Charitéplatz 1 10117 Berlin / DE | 02 /
JINEK, Martin 1846 Spruce Street Berkeley, CA 94709 / US | 03 /
DOUDNA CATE, James Harrison 164 Vicente Road Berkeley, CA 94705 / US | 04 /
LIM, Wendell 149 Collins Street San Francisco, CA 94118 / US | 05 /
QI, Lei 730 Kinkead Way, 302 Albany, CA 94706 / US | 06 /
CHYLINSKI, Krzysztof Simmeringer Hauptstrasse 45/8 1110 Vienna / AT | 07 /
DOUDNA, Jennifer A. 164 Vicente Road Berkeley, CA 94705 / US | [2018/46] | Representative(s) | Maiwald GmbH Elisenhof Elisenstraße 3 80335 München / DE | [N/P] |
Former [2019/14] | Mewburn Ellis LLP City Tower 40 Basinghall Street London EC2V 5DE / GB | ||
Former [2018/46] | Green, Katherine, et al Mewburn Ellis LLP City Tower 40 Basinghall Street London EC2V 5DE / GB | Application number, filing date | 18152360.6 | 15.03.2013 | [2018/46] | Priority number, date | US201261652086P | 25.05.2012 Original published format: US 201261652086 P | US201261716256P | 19.10.2012 Original published format: US 201261716256 P | US201361757640P | 28.01.2013 Original published format: US 201361757640 P | US201361765576P | 15.02.2013 Original published format: US 201361765576 P | [2018/46] | Filing language | EN | Procedural language | EN | Publication | Type: | A1 Application with search report | No.: | EP3401400 | Date: | 14.11.2018 | Language: | EN | [2018/46] | Type: | B1 Patent specification | No.: | EP3401400 | Date: | 03.04.2019 | Language: | EN | [2019/14] | Search report(s) | (Supplementary) European search report - dispatched on: | EP | 21.09.2018 | Classification | IPC: | C12N15/11, C12N15/63, C07K19/00, C12N15/10, C12N15/90, A61K38/46, A61K48/00 | [2018/46] | CPC: |
A61K38/465 (EP,IL,US);
C12N15/907 (GB,IL,KR,US);
C12N15/111 (EP,GB,IL,KR,US);
C12N15/102 (EP,GB,IL,KR,US);
A01H6/4684 (IL,US);
A01K67/027 (IL,US);
A61K48/00 (IL,US);
A61P31/00 (EP,IL);
A61P31/04 (EP,IL);
A61P31/12 (EP,IL);
A61P35/00 (EP,IL);
A61P43/00 (EP,IL);
C12N15/113 (EP,GB,IL,KR,US);
C12N15/63 (EP,GB,IL,KR,US);
C12N15/70 (IL,US);
C12N15/746 (IL,US);
C12N15/90 (GB,IL,KR,US);
C12N15/902 (IL,US);
C12N5/10 (IL,KR);
C12N9/22 (EP,GB,IL,KR,US);
C12Q1/686 (IL,US);
C12Y301/04 (EP,GB,IL,US);
H01L21/02312 (US);
H01L21/02365 (US);
H01L33/0075 (US);
C07K2319/71 (GB,IL);
C07K2319/85 (GB,IL);
C12N2310/11 (GB,IL,KR,US);
C12N2310/13 (GB,IL,KR,US);
C12N2310/14 (IL,US);
C12N2310/20 (EP,IL,US);
C12N2310/31 (IL,US);
C12N2310/32 (IL,US);
C12N2310/33 (IL,US);
C12N2310/3519 (EP,GB,IL,KR,US);
C12N2310/531 (EP,GB,IL,US);
| Designated contracting states | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR [2018/52] |
Former [2018/46] | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR | Extension states | BA | 19.11.2018 | ME | 19.11.2018 | Title | German: | VERFAHREN UND ZUSAMMENSETZUNGEN ZUR RNA-GESTEUERTEN ZIEL-DNA-MODIFIKATION UND ZUR RNA-GESTEUERTEN TRANSKRIPTIONSMODULATION | [2018/46] | English: | METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION | [2018/46] | French: | PROCÉDÉS ET COMPOSITIONS PERMETTANT LA MODIFICATION DE L'ADN CIBLE DIRIGÉE PAR L'ARN ET LA MODULATION DE LA TRANSCRIPTION DIRIGÉE PAR L'ARN | [2018/46] | Examination procedure | 19.11.2018 | Amendment by applicant (claims and/or description) | 19.11.2018 | Examination requested [2018/52] | 19.11.2018 | Date on which the examining division has become responsible | 30.01.2019 | Observations by third parties | 05.02.2019 | Communication of intention to grant the patent | 11.02.2019 | Disapproval of the communication of intention to grant the patent by the applicant or resumption of examination proceedings by the EPO | 11.02.2019 | Fee for grant paid | 11.02.2019 | Fee for publishing/printing paid | 20.02.2019 | Information about intention to grant a patent | 20.02.2019 | Receipt of the translation of the claim(s) | Parent application(s) Tooltip | EP13793997.1 / EP2800811 | EP17163434.8 / EP3241902 | Divisional application(s) | EP19157590.1 / EP3597749 | EP21207127.8 / EP4043564 | EP23187511.3 | Opposition(s) | Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | 02
17.12.2019
02.01.2020
ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE | 03
03.01.2020
15.01.2020
ADMISSIBLE Greaves Brewster LLP Copa House Station Road Cheddar Somerset BS27 3AH / GB | 04
03.01.2020
15.01.2020
ADMISSIBLE HGF Limited 1 City Walk Leeds Yorkshire LS11 9DX / GB Opponent's representative HGF HGF Limited 1 City Walk Leeds LS11 9DX / GB | [N/P] |
Former [2021/43] | |||
Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | ||
02
17.12.2019
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ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE | |||
03
03.01.2020
15.01.2020
ADMISSIBLE Greaves Brewster LLP Copa House Station Road Cheddar Somerset BS27 3AH / GB | |||
04
03.01.2020
15.01.2020
ADMISSIBLE HGF Limited 1 City Walk Leeds Yorkshire LS11 9DX / GB Opponent's representative HGF 1 City Walk Leeds LS11 9DX / GB | |||
Former [2020/30] | |||
Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | ||
02
17.12.2019
02.01.2020
ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE Opponent's representative Weber & Seidel Rechts- und Patentanwälte Handschuhsheimer Landstraße 2a 69120 Heidelberg / DE | |||
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03.01.2020
15.01.2020
ADMISSIBLE Greaves Brewster LLP Copa House Station Road Cheddar Somerset BS27 3AH / GB | |||
04
03.01.2020
15.01.2020
ADMISSIBLE HGF Limited 1 City Walk Leeds Yorkshire LS11 9DX / GB Opponent's representative HGF 1 City Walk Leeds LS11 9DX / GB | |||
Former [2020/28] | |||
Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | ||
02
17.12.2019
02.01.2020
ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE Opponent's representative Weber & Seidel Rechts- und Patentanwälte Handschuhsheimer Landstraße 2a 69120 Heidelberg / DE | |||
03
03.01.2020
15.01.2020
ADMISSIBLE Greaves Brewster LLP Copa House Station Road Cheddar Somerset BS27 3AH / GB | |||
04
03.01.2020
15.01.2020
ADMISSIBLE HGF 1 City Walk Leeds Yorkshire LS11 9DX / GB Opponent's representative HGF 1 City Walk Leeds LS11 9DX / GB | |||
Former [2020/07] | |||
Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | ||
02
17.12.2019
02.01.2020
ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE Opponent's representative Weber & Seidel Rechts- und Patentanwälte Handschuhsheimer Landstraße 2a 69120 Heidelberg / DE | |||
03
03.01.2020
ADMISSIBLE Greaves Brewster LLP Copa House Station Road Cheddar Somerset BS27 3AH / GB | |||
04
03.01.2020
HGF Limited 1 City Walk Leeds Yorkshire LS11 9DX / GB Opponent's representative HGF Limited 1 City Walk Leeds LS11 9DX / GB | |||
Former [2020/04] | |||
Opponent(s) | 01
04.04.2019
08.05.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | ||
02
17.12.2019
ADMISSIBLE Testbiotech e.V. Institut für unabhängige Folgenabschätzung in der Biotechnologie Frohschammerstraße 14 80807 München / DE Opponent's representative Weber & Seidel Rechts- und Patentanwälte Handschuhsheimer Landstraße 2a 69120 Heidelberg / DE | |||
Former [2019/20] | |||
Opponent(s) | 01
04.04.2019
ADMISSIBLE df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte ParG mbB Fünf Höfe Theatinerstrasse 16 80333 München / DE Opponent's representative Pohlman, Sandra M. df-mp Dörries Frank-Molnia & Pohlman Patentanwälte Rechtsanwälte PartG mbB Theatinerstrasse 16 80333 München / DE | 28.01.2020 | Invitation to proprietor to file observations on the notice of opposition | 05.08.2020 | Reply of patent proprietor to notice(s) of opposition | 21.02.2022 | Date of oral proceedings | 25.04.2022 | Despatch of interlocutory decision in opposition | 25.04.2022 | Despatch of minutes of oral proceedings | Appeal following opposition | 04.07.2022 | Appeal received No. T1549/22 | 04.07.2022 | Payment of appeal fee | 05.09.2022 | Statement of grounds filed | 24.06.2022 | Appeal received No. T1549/22 | 24.06.2022 | Payment of appeal fee | 05.09.2022 | Statement of grounds filed | 13.06.2022 | Appeal received No. T1549/22 | 13.06.2022 | Payment of appeal fee | 05.09.2022 | Statement of grounds filed | 04.07.2022 | Appeal received No. T1549/22 | 01.09.2022 | Statement of grounds filed | 16.10.2024 | Date of oral proceedings | Fees paid | Renewal fee | 12.02.2018 | Renewal fee patent year 03 | 12.02.2018 | Renewal fee patent year 04 | 12.02.2018 | Renewal fee patent year 05 | 27.03.2018 | Renewal fee patent year 06 | 08.02.2019 | Renewal fee patent year 07 |
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Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court. | Lapses during opposition Tooltip | SM | 03.04.2019 | [2020/14] | Documents cited: | Search | [A]WO2010021692 (SANGAMO BIOSCIENCES INC [US], et al) [A] 1-23 * the whole document *; | [A]WO2011072246 (UNIV MINNESOTA [US], et al) [A] 1-23 * the whole document *; | [E]WO2014065596 (TOOLGEN INC [KR]) [E] 1-23 * the whole document *; | [E]WO2014089290 (SIGMA ALDRICH CO LLC [US], et al) [E] 1-23 * the whole document *; | [E]WO2014093661 (BROAD INST INC [US], et al) [E] 1-23 * the whole document *; | [E]WO2014093712 (BROAD INST INC [US], et al) [E] 1-23 * the whole document *; | [E]WO2014099744 (HARVARD COLLEGE [US]) [E] 1-23* the whole document *; | [A] - PAPWORTH M ET AL, "Designer zinc-finger proteins and their applications", GENE, ELSEVIER, AMSTERDAM, NL, vol. 366, no. 1, doi:10.1016/J.GENE.2005.09.011, ISSN 0378-1119, (20060117), pages 27 - 38, (20060117), XP024934269 [A] 1-23 * the whole document * DOI: http://dx.doi.org/10.1016/j.gene.2005.09.011 | [A] - ELITZA DELTCHEVA ET AL, "CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III", NATURE, (20110331), vol. 471, no. 7340, doi:10.1038/nature09886, ISSN 0028-0836, pages 602 - 607, XP055308803 [A] 1-23 * the whole document * DOI: http://dx.doi.org/10.1038/nature09886 | [A] - MAKAROVA KIRA S ET AL, "Evolution and classification of the CRISPR-Cas systems", NATURE REVIEWS. MICROBIO, NATURE PUBLISHING GROUP, GB, (20110509), vol. 9, no. 6, doi:10.1038/NRMICRO2577, ISSN 1740-1526, pages 467 - 477, XP009155547 [A] 1-23 * the whole document * DOI: http://dx.doi.org/10.1038/nrmicro2577 | [A] - BLAKE WIEDENHEFT ET AL, "RNA-guided genetic silencing systems in bacteria and archaea", NATURE, (20120215), vol. 482, no. 7385, doi:10.1038/nature10886, ISSN 0028-0836, pages 331 - 338, XP055116249 [A] 1-23 * the whole document * DOI: http://dx.doi.org/10.1038/nature10886 | [XPI] - M. JINEK ET AL, "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity", SCIENCE, (20120817), vol. 337, no. 6096, doi:10.1126/science.1225829, ISSN 0036-8075, pages 816 - 821, XP055299674 [XP] 11-14,18,19,22 * the whole document * [I] 1-23 DOI: http://dx.doi.org/10.1126/science.1225829 | [P] - M. JINEK ET AL, "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity (Supplementary Material)", SCIENCE, US, (20120628), vol. 337, no. 6096, doi:10.1126/science.1225829, ISSN 0036-8075, page 821, XP055067747 [P] * the whole document * DOI: http://dx.doi.org/10.1126/science.1225829 | [XPI] - L. CONG ET AL, "Multiplex Genome Engineering Using CRISPR/Cas Systems", SCIENCE, (20130215), vol. 339, no. 6121, doi:10.1126/science.1231143, ISSN 0036-8075, pages 819 - 823, XP055067741 [XP] 1,3-7,9-14,16,18,19,22 * the whole document * [I] 1-23 DOI: http://dx.doi.org/10.1126/science.1231143 | [P] - L. CONG ET AL, "Supplementary Material to : Multiplex Genome Engineering Using CRISPR/Cas Systems", SCIENCE, (20130103), vol. 339, no. 6121, doi:10.1126/science.1231143, ISSN 0036-8075, pages 819 - 823, XP055067744 [P] * the whole document * DOI: http://dx.doi.org/10.1126/science.1231143 | [XPI] - P. MALI ET AL, "RNA-Guided Human Genome Engineering via Cas9", SCIENCE, (20130103), vol. 339, no. 6121, doi:10.1126/science.1232033, ISSN 0036-8075, pages 823 - 826, XP055111247 [XP] 1,3-7,9-14,16,18,19,22 * the whole document * [I] 1-23 DOI: http://dx.doi.org/10.1126/science.1232033 | [P] - P. Mali ET AL, "Supplementary information for RNA-Guided Human Genome Engineering via Cas9 (XP 055337932)", Science, (20130103), vol. 339, no. 6121, doi:10.1126/science.1232033, ISSN 0036-8075, pages 823 - 826, XP055403737 [P] * the whole document * DOI: http://dx.doi.org/10.1126/science.1232033 | [XPI] - MARTIN JINEK ET AL, "RNA-programmed genome editing in human cells", E-LIFE, SAM LTD, GB, vol. 2, doi:10.7554/ELIFE.00471, ISSN 2050-084X, (20130129), pages e00471 - 1, (20130628), XP002699851 [XP] 1,3-7,9-14,16,18,19,22 * the whole document * [I] 1-23 DOI: http://dx.doi.org/10.7554/eLife.00471 | [P] - Martin Jinek ET AL, "RNA-programmed genome editing in human cells (Figures and figure supplements)", eLife, (20130129), vol. 2, doi:10.7554/eLife.00471, XP055167481 [P] * the whole document * DOI: http://dx.doi.org/10.7554/eLife.00471 | by applicant | US3687808 | US5034506 | WO9303769 | WO9309239 | US5222982 | WO9319191 | WO9412649 | WO9428938 | WO9500655 | US5385582 | WO9511984 | WO9516783 | US5451513 | US5489677 | US5539082 | US5545817 | US5545818 | US5576198 | US5602240 | US5714331 | US5719262 | WO9839352 | US5843780 | WO9914226 | WO9920741 | US6200806 | WO0118048 | WO0151616 | US2003022831 | US2003032593 | WO03020920 | US2003083256 | US2003220334 | US7029913 | US7078387 | US7153684 | US7169874 | US2007254842 | US2008081064 | US2009047263 | US2009068742 | US2009191159 | US2009196903 | US2009227032 | US2009246875 | US2009304646 | - ALTSCHUL et al., J. Mol. Biol., (19900000), vol. 215, pages 403 - 410 | - ZHANG; MADDEN, Genome Res., (19970000), vol. 7, pages 649 - 656 | - SMITH; WATERMAN, Adv. Appl. Math., (19810000), vol. 2, pages 482 - 489 | - ALTSCHUL et al., J. Mol. Bioi., (19900000), vol. 215, pages 403 - 10 | - MIYAGISHI et al., Nature Biotechnology, (20020000), vol. 20, pages 497 - 500 | - XIA et al., Nucleic Acids Res., (20030901), vol. 31, no. 17 | - CHEN et al., Cell, (19870000), vol. 51, pages 7 - 19 | - LLEWELLYN et al., Nat. Med., (20100000), vol. 16, no. 10, pages 1161 - 1166 | - OH et al., Gene Ther, (20090000), vol. 16, page 437 | - SASAOKA et al., Mol. Brain Res., (19920000), vol. 16, page 274 | - BOUNDY et al., J. Neurosci., (19980000), vol. 18, page 9989 | - KANEDA et al., Neuron, (19910000), vol. 6, pages 583 - 594 | - RADOVICK et al., Proc. Natl. Acad. Sci. USA, (19910000), vol. 88, pages 3402 - 3406 | - OBERDICK et al., Science, (19900000), vol. 248, pages 223 - 226 | - BARTGE et al., Proc. Natl. Acad. Sci. USA, (19880000), vol. 85, pages 3648 - 3652 | - COMB et al., EMBO J., (19880000), vol. 17, pages 3793 - 3805 | - MAYFORD et al., Proc. Natl. Acad. Sci. USA, (19960000), vol. 93, page 13250 | - CASANOVA et al., Genesis, (20010000), vol. 31, page 37 | - LIU et al., Gene Therapy, (20040000), vol. 11, pages 52 - 60 | - TOZZO et al., Endocrinol, (19970000), vol. 138, page 1604 | - ROSS et al., Proc. Natl. Acad. Sci. USA, (19900000), vol. 87, page 9590 | - PAVJANI et al., Nat. Med., (20050000), vol. 11, page 797 | - KNIGHT et al., Proc. Natl. Acad. Sci. USA, (20030000), vol. 100, page 14725 | - KURIKI et al., Biol. Pharm. Bull., (20020000), vol. 25, page 1476 | - SATO et al., J. Biol. Chem., (20020000), vol. 277, page 15703 | - TABOR et al., J. Biol. Chem., (19990000), vol. 274, page 20603 | - MASON et al., Endocrinol, (19980000), vol. 139, page 1013 | - CHEN et al., Biochem. Biophys. Res. Comm., (19990000), vol. 262, page 187 | - KITA et al., Biochem. Biophys. Res. Comm., (20050000), vol. 331, page 484 | - CHAKRABARTI, Endocrinol, (20100000), vol. 151, page 2408 | - PLATT et al., Proc. Natl. Acad. Sci. USA, (19890000), vol. 86, page 7490 | - SEO et al., Molec. Endocrinol., (20030000), vol. 17, page 1522 | - FRANZ et al., Cardiovasc. Res., (19970000), vol. 35, pages 560 - 566 | - ROBBINS et al., Ann. N.Y. Acad. Sci., (19950000), vol. 752, pages 492 - 505 | - LINN et al., Circ. Res., (19950000), vol. 76, pages 584 - 591 | - PARMACEK et al., Mol. Cell. Biol., (19940000), vol. 14, pages 1870 - 1885 | - HUNTER et al., Hypertension, (19930000), vol. 22, pages 608 - 617 | - SARTORELLI et al., Proc. Natl. Acad. Sci. USA, (19920000), vol. 89, pages 4047 - 4051 | - AKYIIREK et al., Mol. Med., (20000000), vol. 6, page 983 | - KIM et al., Mol. Cell. Biol., (19970000), vol. 17, pages 2266 - 2278 | - LI et al., J. Cell Biol., (19960000), vol. 132, pages 849 - 859 | - MOESSLER et al., Development, (19960000), vol. 122, pages 2415 - 2425 | - YOUNG et al., Ophthalmol. Vis. Sci., (20030000), vol. 44, page 4076 | - NICOUD et al., J. Gene Med., (20070000), vol. 9, page 1015 | - YOKOYAMA et al., Exp Eye Res., (19920000), vol. 55, page 225 | - PANYAM, Adv Drug Deliv Rev., (20120913), vol. S0169-40, no. 12, pages 00283 - 9 | - MORRISON et al., Cell, (19970000), vol. 88, pages 287 - 298 | - THOMSON, Science, (19981106), vol. 282, no. 5391, pages 1145 - 7 | - TAKAHASHI, Cell, (20071130), vol. 131, no. 5, pages 861 - 72 | - TAKAHASHI, Nat Protoc., (20070000), vol. 2, no. 12, pages 3081 - 9 | - YU, Science, (20071221), vol. 318, no. 5858, pages 1917 - 20 | - THOMSON et al., Science, (19980000), vol. 282, page 1145 | - THOMSON et al., Proc. Natl. Acad. Sci USA, (19950000), vol. 92, page 7844 | - THOMSON et al., Biol. Reprod., (19960000), vol. 55, page 254 | - SHAMBLOTT et al., Proc. Natl. Acad. Sci. USA, (19980000), vol. 95, page 13726 | - MATSUI, Y. et al., Cell, (19920000), vol. 70, page 841 | - SHAMBLOTT, M. et al., Proc. Natl. Acad. Sci. USA, (20010000), vol. 98, page 113 | - SHAMBLOTT, M. et al., Proc. Natl. Acad. Sci. USA, (19980000), vol. 95, page 13726 | - KOSHIMIZU, U. et al., Development, (19960000), vol. 122, page 1235 | - NAKAMURA et al., Genes Cells, (20120500), vol. 17, no. 5, pages 344 - 64 | - VAVALLE et al., Future Cardiol., (20120500), vol. 8, no. 3, pages 371 - 82 | - CITARTAN et al., Biosens Bioelectron, (20120415), vol. 34, no. 1, pages 1 - 11 | - LIBERMAN et al., Wiley Interdiscip Rev RNA, (20120500), vol. 3, no. 3, pages 369 - 84 | - DWAINE A. BRAASCH; DAVID R. COREY, Biochemistry, (20020000), vol. 41, no. 14, pages 4503 - 4510 | - WANG et al., J. Am. Chem. Soc., (20000000), vol. 122, pages 8595 - 8602 | - SINGH et al., Chem. Commun., (19980000), vol. 4, pages 455 - 456 | - WAHLESTEDT et al., Proc. Natl. Acad. Sci. U.S.A., (20000000), vol. 97, pages 5633 - 5638 | - KOSHKIN et al., Tetrahedron, (19980000), vol. 54, pages 3607 - 3630 | - MARTIN et al., Helv. Chim. Acta, (19950000), vol. 78, pages 486 - 504 | - Kroschwitz, J. I., The Concise Encyclopedia Of Polymer Science And Engineering, John Wiley & Sons, (19900000), pages 858 - 859 | - ENGLISCH et al., Angewandte Chemie, International Edition, (19910000), vol. 30, page 613 | - SANGHVI, Y. S., "Chapter 15", SANGHVI, Y. S., Crooke, S. T. and Lebleu, B., Antisense Research and Applications, CRC Press, (19930000), pages 289 - 302 | - Sanghvi et al., Antisense Research and Applications, CRC Press, (19930000), pages 276 - 278 | - LETSINGER et al., Proc. Natl. Acad. Sci. USA, (19890000), vol. 86, pages 6553 - 6556 | - MANOHARAN et al., Bioorg. Med. Chem. Let., (19940000), vol. 4, pages 1053 - 1060 | - MANOHARAN et al., Ann. N.Y. Acad. Sci., (19920000), vol. 660, pages 306 - 309 | - MANOHARAN et al., Bioorg. Med. Chem. Let., (19930000), vol. 3, pages 2765 - 2770 | - OBERHAUSER et al., Nucl. Acids Res., (19920000), vol. 20, pages 533 - 538 | - SAISON-BEHMOARAS et al., EMBO J., (19910000), vol. 10, pages 1111 - 1118 | - KABANOV et al., FEBS Lett., (19900000), vol. 259, pages 327 - 330 | - SVINARCHUK et al., Biochimie, (19930000), vol. 75, pages 49 - 54 | - MANOHARAN et al., Tetrahedron Lett., (19950000), vol. 36, pages 3651 - 3654 | - SHEA et al., Nucl. Acids Res., (19900000), vol. 18, pages 3777 - 3783 | - MANOHARAN et al., Nucleosides & Nucleotides, (19950000), vol. 14, pages 969 - 973 | - MISHRA et al., Biochim. Biophys. Acta, (19950000), vol. 1264, pages 229 - 237 | - CROOKE et al., J. Pharmacol. Exp. Ther., (19960000), vol. 277, pages 923 - 937 | - ZENDER et al., Cancer Gene Ther., (20020000), vol. 9, no. 6, pages 489 - 96 | - NOGUCHI et al., Diabetes, (20030000), vol. 52, no. 7, pages 1732 - 1737 | - TREHIN et al., Pharm. Research, (20040000), vol. 21, pages 1248 - 1256 | - WENDER et al., Proc. Natl. Acad. Sci. USA, (20000000), vol. 97, pages 13003 - 13008 | - AGUILERA et al., Integr Biol (Camb, (20090600), vol. 1, no. 5-6, pages 371 - 381 | - LI et al., Invest Opthalmol Vis Sci, (19940000), vol. 35, pages 2543 - 2549 | - BORRAS et al., Gene Ther, (19990000), vol. 6, page 515 524 | - LI; DAVIDSON, PNAS, (19950000), vol. 92, page 7700 7704 | - SAKAMOTO et al., H Gene Ther, (19990000), vol. 5, page 1088 1097 | - ALI et al., Hum Gene Ther, (19980000), vol. 9, page 81 86 | - FLANNERY et al., PNAS, (19970000), vol. 94, page 6916 6921 | - BENNETT et al., Invest Opthalmol Vis Sci, (19970000), vol. 38, page 2857 2863 | - JOMARY et al., Gene Ther, (19970000), vol. 4, page 683 690 | - ROLLING et al., Hum Gene Ther, (19990000), vol. 10, page 641 648 | - ALI et al., Hum Mol Genet, (19960000), vol. 5, page 591 594 | - SAMULSKI et al., J. Vir., (19890000), vol. 63, pages 3822 - 3828 | - MENDELSON et al., Virol., (19880000), vol. 166, pages 154 - 165 | - FLOTTE et al., PNAS, (19930000), vol. 90, pages 10613 - 10617 | - MIYOSHI et al., PNAS, (19970000), vol. 94, page 10319 23 | - TAKAHASHI et al., J Virol, (19990000), vol. 73, page 7812 7816 | - BITTER et al., Methods in Enzymology, (19870000), vol. 153, pages 516 - 544 | - PANYAM, Adv Drug Deliv Rev, (20120913), vol. S0169-40, no. 12, pages 00283 - 9 | - KAWAI et al., "Transformation of Saccharomyces cerevisiae and other fungi: methods and possible underlying mechanism", Bioeng Bugs., (20101100), vol. 1, no. 6, pages 395 - 403 | - TANKA et al., Nature, (20040318), vol. 428, no. 6980, pages 323 - 8 | - ANGEL; YANIK, PLoS ONE, (20100000), vol. 5, no. 7, page el 1756 | - BEUMER et al., "Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases", PNAS, (20080000), vol. 105, no. 50, pages 19821 - 19826 | - FUTAKI et al., Curr Protein Pept Sci., (20030400), vol. 4, no. 2, pages 87 - 9,446 | - WENDER et al., Proc. Natl. Acad. Sci. U.S.A, (20001121), vol. 97, no. 24, pages 13003 - 8 | - CHANG et al., Proc. Natl. Acad Sci USA, (19870000), vol. 84, pages 4959 - 4963 | - NEHLS et al., Science, (19960000), vol. 272, pages 886 - 889 | - LANGER, Science, (19900000), vol. 249, pages 1527 - 1533 | - GAMA et al., Brain Struct Funct, (20100300), vol. 214, no. 2-3, pages 91 - 109 | - HUSAINI et al., GM Crops, (20110601), vol. 2, no. 3, pages 150 - 62 | - KLEIN et al., Nature, (19870000), vol. 327, pages 70 - 73 | - HERRERA-ESTRELLA et al., Nature, (19830000), vol. 303, page 209 | - BEVAN, Nucl Acid Res, (19840000), vol. 12, pages 8711 - 8721 | - KLEE, Bio/Technolo, (19850000), vol. 3, pages 637 - 642 | - CHRISTOU, Bio/Technology, (19910000), vol. 9, pages 957 - 4462 | - GORDON-KAMM, Plant Cell, (19900000), vol. 2, pages 603 - 618 | - WEEKS et al., Plant Physiol, (19930000), vol. 102, pages 1077 - 1084 | - VASIL, Bio/Technolo, (19930000), vol. 10, pages 667 - 674 | - WAN; LEMEAUX, Plant Physiol, (19940000), vol. 104, pages 37 - 48 | - ISHIDA et al., Nature Biotech, (19960000), vol. 14, pages 745 - 750 | - DANIELI et al., Nat. Biotechnol, (19980000), vol. 16, pages 345 - 348 | - STAUB et al., Nat. Biotechnol, (20000000), vol. 18, pages 333 - 338 | - O'NEILL et al., Plant J., (19930000), vol. 3, pages 729 - 738 | - KNOBLAUCH et al., Nat. Biotechnol, vol. 17, pages 906 - 909 | - BOYNTON et al., Methods in Enzymology, (19930000), vol. 217, pages 510 - 536 | - SVAB et al., Proc. Natl. Acad. Sci. USA, (19930000), vol. 90, pages 913 - 917 | - MCBRIDE et al., Proc. Nati. Acad. Sci. USA, (19940000), vol. 91, pages 7301 - 7305 | - CITARTAN et al., Biosens Bioelectron., (20120415), vol. 34, no. 1, pages 1 - 11 | - DOHMEN et al., Science, (19940000), vol. 263, no. 5151, pages 1273 - 1276 | - SCHOEBER et al., Am J Physiol Renal Physiol., (20090100), vol. 296, no. 1, pages F204 - 11 | - CHU et al., Bioorg Med Chem Lett., (20081115), vol. 18, no. 22, pages 5941 - 4 | - YANG et al., Mol Cell, (20121130), vol. 48, no. 4, pages 487 - 8 | - BARBOUR et al., Biosci Rep, (20130118), vol. 33, no. 1 | - LI et al., Invest Opthalmol Vis Sci, (19940000), vol. 35, page 2543 2549 | - LI; DAVIDSON, PNAS, (19950000), vol. 92, pages 7700 - 7704 | - JOMARY et al., Gene Ther, (19970000), vol. 4, pages 683 - 690 | - ALI et al., Hum Mol Genet, (19960000), vol. 5, pages 591 - 594 | - YOKOYAMA et al., Exp Eye Res, (19920000), vol. 55, page 225 | - B. WIEDENHEFT; S. H. STERNBERG; J. A. DOUDNA, Nature, (20120000), vol. 482, page 331 | - D. BHAYA; M. DAVISON; R. BARRANGOU, Annu. Rev. Genet., (20110000), vol. 45, page 273 | - M. P. TERNS; R. M. TERNS, Curr. Opin. Microbiol., (20110000), vol. 14, page 321 | - E. DELTCHEVA et al., Nature, (20110000), vol. 471, page 602 | - J. CARTE; R. WANG; H. LI; R. M. TERNS; M. P. TERNS, Genes Dev, (20080000), vol. 22, page 3489 | - R. E. HAURWITZ; M. JINEK; B. WIEDENHEFT; K. ZHOU; J. A. DOUDNA, Science, (20100000), vol. 329, page 1355 | - R. WANG; G. PREAMPLUME; M. P. TERNS; R. M. TERNS; H. LI, Structure, (20110000), vol. 19, page 257 | - E. M. GESNER; M. J. SCHELLENBERG; E. L. GARSIDE; M. M. GEORGE; A. M. MACMILLAN, Nat. Struct. Mol. Biol., (20110000), vol. 18, page 688 | - A. HATOUM-ASLAN; I. MANIV; L. A. MARRAFFINI, Proc. Natl. Acad. Sci. U.S.A., (20110000), vol. 108, page 21218 | - S. J. J. BROUNS et al., Science, (20080000), vol. 321, page 960 | - D. G. SASHITAL; M. JINEK; J. A. DOUDNA, Nat. Struct. Mol. Biol., (20110000), vol. 18, page 680 | - N. G. LINTNER et al., J. Biol. Chem., (20110000), vol. 286, page 21643 | - E. SEMENOVA et al., Proc. Natl. Acad. Sci. U.S.A., (20110000), vol. 108, page 10098 | - B. WIEDENHEFT et al., Proc. Natl. Acad. Sci. U.S.A., (20110000), vol. 108, page 10092 | - B. WIEDENHEFT et al., Nature, (20110000), vol. 477, page 486 | - C. R. HALE et al., Cell, (20090000), vol. 139, page 945 | - J. A. L. HOWARD; S. DELMAS; I. IVANCIC-BACE; E. L. BOLT, Biochem. J., (20110000), vol. 439, page 85 | - E. R. WESTRA et al., Mol. Cell, (20120000), vol. 46, page 595 | - C. R. HALE et al., Mol. Cell, (20120000), vol. 45, page 292 | - J. ZHANG et al., Mol. Cell, (20120000), vol. 45, page 303 | - K. S. MAKAROVA et al., Nat. Rev. Microbiol., (20110000), vol. 9, page 467 | - K. S. MAKAROVA; N. V. GRISHIN; S. A. SHABALINA; Y. I. WOLF; E. V. KOONIN, Biol. Direct, (20060000), vol. 1, page 7 | - K. S. MAKAROVA; L. ARAVIND; Y. I. WOLF; E. V. KOONIN, Biol. Direct, (20110000), vol. 6, page 38 | - S. GOTTESMAN, Nature, (20110000), vol. 471, page 588 | - R. BARRANGOU et al., Science, (20070000), vol. 315, page 1709 | - J. E. GARNEAU et al., Nature, (20100000), vol. 468, page 67 | - R. SAPRANAUSKAS et al., Nucleic Acids Res., (20110000), vol. 39, page 9275 | - G. K. TAYLOR; D. F. HEITER; S. PIETROKOVSKI; B. L. STODDARD, Nucleic Acids Res., (20110000), vol. 39, page 9705 | - H. DEVEAU et al., J. Bacteriol., (20080000), vol. 190, page 1390 | - B. P. LEWIS; C. B. BURGE; D. P. BARTEL, Cell, (20050000), vol. 120, page 15 | - G. HUTVAGNER; M. J. SIMARD, Nat. Rev. Mol. Cell Biol., (20080000), vol. 9, page 22 | - F. J. M. MOJICA; C. DIEZ-VILLASENOR; J. GARCIA-MARTINEZ; C. ALMENDROS, Microbiology, (20090000), vol. 155, page 733 | - L. A. MARRAFFINI; E. J. SONTHEIMER, Nature, (20100000), vol. 463, page 568 | - D. G. SASHITAL; B. WIEDENHEFT; J. A. DOUDNA, Mol. Cell, (20120000), vol. 46, page 606 | - M. CHRISTIAN et al., Genetics, (20100000), vol. 186, page 757 | - J. C. MILLER et al., Nat. Biotechnol., (20110000), vol. 29, page 143 | - F. D. URNOV; E. J. REBAR; M. C. HOLMES; H. S. ZHANG; P. D. GREGORY, Nat. Rev. Genet., (20100000), vol. 11, page 636 | - D. CARROLL, Gene Ther, (20080000), vol. 15, page 1463 | - M. G. CAPARON; J. R. SCOTT, "Genetic manipulation of pathogenic streptococci", Methods Enzymol., (19910000), vol. 204, page 556 | - C. FR0KJSER-JENSEN et al., "Single-copy insertion of transgenes in Caenorhabditis elegans", Nat. Genet., (20080000), vol. 40, page 1375 | - R. B. DENMAN, "Using RNAFOLD to predict the activity of small catalytic RNAs", Biotechniques, (19930000), vol. 15, page 1090 | - I. L. HOFACKER; P. F. STADLER, "Memory efficient folding algorithms for circular RNA secondary structures", Bioinformatics, (20060000), vol. 22, page 1172 | - K. DARTY; A. DENISE; Y. PONTY, "VARNA: Interactive drawing and editing of the RNA secondary structure", Bioinformatics, (20090000), vol. 25, doi:doi:10.1093/bioinformatics/btp250, page 1974, XP055198531 DOI: http://dx.doi.org/10.1093/bioinformatics/btp250 | - GRISSA I et al., BMC Bioinformatics, (20070000), vol. 8, page 172 | - GenBank, Database accession no. NC_002163 | - GenBank, Database accession no. NC_008601 | - GenBank, Database accession no. NC_003116 | - GenBank, Database accession no. NC_003212 | - GenBank, Database accession no. NC_004350 | Opposition | WO2014089290 | WO2014093595 | EP2825654 | US106048 | WO2011072246 | WO2013176772 | WO2014065596 | WO2014093712 | WO2014093661 | WO2014093655 | WO2014093635 | WO2014093622 | WO2014093701 | WO2014093709 | WO2014093718 | WO2014099744 | EP3401400 | - JINEK M et al., "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity", Science, (20120817), pages 816 - 821, XP055067740 DOI: http://dx.doi.org/10.1126/science.1225829 | - Jinek et al., "Supplementary Materials for A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity", SCIENCE, (2012), pages 1 - 37, XP055067747 DOI: http://dx.doi.org/10.1126/science.1225829 | - CONG L et al., "Multiplex Genome Engineering Using CRISPR/Cas Systems", Science, (20130103), XP055458249 DOI: http://dx.doi.org/10.1126/science.1231143 | - Cong et al., "Supplementary Material to : Multiplex Genome Engineering Using CRISPR/Cas Systems", SCIENCE, (2013), pages 1 - 28, XP055067744 DOI: http://dx.doi.org/10.1126/science.1231143 | - MALI P et al., "RNA-Guided Human Genome Engineering via Cas9", Science, (20130103), XP055111247 DOI: http://dx.doi.org/10.1126/science.1232033 | - Mali et al., "Supplementary Materials for RNA-Guided Human Genome Engineering via Cas9", SCIENCE, (20130215), pages 1 - 36, XP002723674 DOI: http://dx.doi.org/10.1126/science.1232033 | - JINEK M et al., "RNA-programmed genome editing in human cells", eLife, (20130129), pages 1 - 9, XP002699851 DOI: http://dx.doi.org/10.7554/eLife.00471 | - DELTCHEVA et al., "CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III", Nature, (20110301), vol. 471, pages 602 - 609, XP055619637 DOI: http://dx.doi.org/10.1038/nature09886 | - MOJICA et al., "Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements", J Mol Evolution, (20050000), vol. 60, pages 174 - 182, XP019363173 DOI: http://dx.doi.org/10.1007/s00239-004-0046-3 | - POURCEL et al., "CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies", Microbiology, (20050000), vol. 151, pages 653 - 663, XP002460396 DOI: http://dx.doi.org/10.1099/mic.0.27437-0 | - BARRANGOU et al., "CRISPR provides acquired resistance against viruses in prokaryotes", Science, (20070000), vol. 315, pages 1709 - 1712, XP002428071 DOI: http://dx.doi.org/10.1126/science.1138140 | - BROUNS et al., "Small CRISPR RNAs guide antiviral defense in prokaryotes", Science, (20080000), vol. 321, pages 960 - 964, XP002559962 DOI: http://dx.doi.org/10.1126/science.1159689 | - MARRAFFINI et al., "CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA", Science, (20080000), vol. 322, no. 5909, pages 1843 - 1845, XP055613684 DOI: http://dx.doi.org/10.1126/science.1165771 | - MAKAROVA et al., "Evolution and classification of the CRISPR-Cas systems", Nature Reviews Microbiology, (20110000), vol. 9, pages 467 - 477, XP009155547 DOI: http://dx.doi.org/10.1038/nrmicro2577 | - SAPRANAUSKAS et al., "THE STREPTOCOCCUS THERMOPHILUS CRISPR/CAS SYSTEM PROVIDES IMMUNITY IN ESCHERICHIA COLI", Nucleic Acid Research, (20110000), vol. 39, no. 21, pages 9275 - 9282, XP055067807 DOI: http://dx.doi.org/10.1093/nar/gkr606 | - Sapranauskas et al., "Supplementary data to The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli", Nucleic Acids Research, (20111101), vol. 39, no. 11, pages 1 - 10, XP055067807 DOI: http://dx.doi.org/10.1093/nar/gkr606 | - KUNIN, V et al., "Evolutionary conservation of sequence and secondary structures in CRISPR repeats", Genome biology, (20070000), vol. 8, pages 61.1 - 61.7, XP021027392 DOI: http://dx.doi.org/10.1186/gb-2007-8-4-r61 | - OLKE C . UHLENBECK, "Tetraloops and RNA folding", Nature, vol. 346, pages 613 - 614, XP055613699 DOI: http://dx.doi.org/10.1038/346613a0 | - HENDRIX et al., "RNA structural motifs: building blocks of a modular biomolecule", Quarterly Reviews of Biophysics, (20050000), vol. 3, no. 38, pages 221 - 243, XP009098023 DOI: http://dx.doi.org/10.1017/S0033583506004215 | - VARANI, "Exceptionally Stable Nucleic Acid Hairpins", Annu. Rev. Biophys. Biomol. Struct., (19950000), vol. 24, pages 379 - 404, XP055613701 DOI: http://dx.doi.org/10.1146/annurev.bb.24.060195.002115 | - LAMBOWITZ et al., "Group // Introns: Mobil Ribozymes that Invade DNA", Cold Spring Harb Perspect Biol, (20110000), vol. 3, page a003616, XP055514471 DOI: http://dx.doi.org/10.1101/cshperspect.a003616 | - Makarova et al., "Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems", Biology Direct, pages 1 - 27, XP021105829 DOI: http://dx.doi.org/10.1186/1745-6150-6-38 | - GARNEAU et al., "The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA", Nature, (20100000), vol. 468, no. 7320, doi:10.1038/nature09523, pages 67 - 71, XP055181397 DOI: http://dx.doi.org/10.1038/nature09523 | - YU B, "RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells", PNAS, (20020000), vol. 99, no. 9, doi:10.1073/pnas.092143499, pages 6047 - 6052, XP002332096 DOI: http://dx.doi.org/10.1073/pnas.092143499 | - MASTROIANNI et al., "Group // Intron-Based Gene Targeting Reactions in Eukaryotes", PLoS ONE, (20080000), vol. 3, no. 9, pages 1 - 15, XP055149290 DOI: http://dx.doi.org/10.1371/journal.pone.0003121 | - ZIMMERLY et al., "Group // Intron Mobility Occurs by Target DNA-Primed Reverse Transcription", Cell, (19950000), vol. 82, doi:10.1016/0092-8674(95)90027-6, pages 545 - 554, XP002911793 DOI: http://dx.doi.org/10.1016/0092-8674(95)90027-6 | - YANG et al., "Efficient integration of an intron RNA into double-stranded DNA by reverse splicing", Nature, (19960000), vol. 381, doi:10.1038/381332a0, pages 332 - 335, XP002918949 DOI: http://dx.doi.org/10.1038/381332a0 | - ROMANI et al., "Hormonal regulation of Mg2+ transport and homeostasis in eukaryotic cells", BioMetals, (20020000), vol. 15, pages 271 - 283, XP055613801 | - O'NEILL et al., "Nucleosome Arrays Inhibit Both Initiation and Elongation of Transcripts by Bacteriophage T7 RNA Polymerase", J. Mol. Biol., (19920000), vol. 223, doi:10.1016/0022-2836(92)90716-W, pages 67 - 78, XP024018312 DOI: http://dx.doi.org/10.1016/0022-2836(92)90716-W | - WIRTZ et al., "Regulated processive transcription of chromatin by T7 RNA polymerase in Trypanosoma brucei", Nucleic Acids Res., (19980000), vol. 26, no. 20, doi:10.1093/nar/26.20.4626, pages 4626 - 4634, XP000872845 DOI: http://dx.doi.org/10.1093/nar/26.20.4626 | - MCCALL et al., "Probes of chromatin accessibility in the Drosophila bithorax complex respond differently to Polycomb-mediated repression", EMBO J., (19960000), vol. 15, no. 3, doi:10.1002/j.1460-2075.1996.tb00389.x, pages 569 - 580, XP055613797 DOI: http://dx.doi.org/10.1002/j.1460-2075.1996.tb00389.x | - JENUWEIN et al., "The immunoglobulin µ enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation", Genes & Dev., (19930000), vol. 7, doi:10.1101/gad.7.10.2016, pages 2016 - 2032, XP055336949 DOI: http://dx.doi.org/10.1101/gad.7.10.2016 | - KOSEKI et al., "Factors governing the activity in vivo of ribozymes transcribed by RNA polymerase III", J. Virology, (19990000), vol. 73, pages 1868 - 1877, XP001027031 DOI: http://dx.doi.org/10.1128/JVI.73.3.1868-1877.1999 | - LINK et al., "Engineering ligand-responsive gene -control elements: lessons learned from natural riboswitches", Gene Therapy, (20090000), vol. 16, doi:10.1038/gt.2009.81, pages 1189 - 1201, XP008148752 DOI: http://dx.doi.org/10.1038/gt.2009.81 | - STERNBERG et al., "Bacteriophage P1 site-specific recombination . I . Recombination between loxP sites", J. Mol. Biol., (19810000), vol. 150, doi:10.1016/0022-2836(81)90375-2, pages 467 - 486, XP024013080 DOI: http://dx.doi.org/10.1016/0022-2836(81)90375-2 | - STERNBERG et al., "Bacteriophage P1 site-specific recombination. II. Recombination between loxP and the bacterial chromosome", J. Mol. Biol., (19810000), vol. 150, doi:10.1016/0022-2836(81)90376-4, pages 487 - 507, XP024013081 DOI: http://dx.doi.org/10.1016/0022-2836(81)90376-4 | - SAUER et al., "Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1", Proc. Nat'l Acad. Sci. USA, (19880000), vol. 85, doi:10.1073/pnas.85.14.5166, pages 5166 - 5170, XP000615552 DOI: http://dx.doi.org/10.1073/pnas.85.14.5166 | - LOONSTRA et al., "Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells", Proc. Nat'l Acad. Sci. USA, (20010000), vol. 98, doi:10.1073/pnas.161269798, pages 9209 - 9214, XP055613805 DOI: http://dx.doi.org/10.1073/pnas.161269798 | - HEIDMANN et al., "Reduction of Cre recombinase toxicity in proliferating Drosophila cells by estrogen-dependent activity regulation", Dev. Genes & Evolution, (20010000), vol. 211, doi:10.1007/s004270100167, pages 458 - 465, XP055613807 DOI: http://dx.doi.org/10.1007/s004270100167 | - SCHMIDT et al., "Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids", Proc. Nat'l Acad. Sci. USA, (20000000), vol. 97, doi:10.1073/pnas.240471297, pages 13702 - 13707, XP002607632 DOI: http://dx.doi.org/10.1073/pnas.240471297 | - COPPOOLSE et al., "Cre recombinase expression can result in phenotypic aberrations in plants", Plant Molecular Biology, (20030000), vol. 51, doi:10.1023/A:1021174726070, pages 263 - 279, XP019262394 DOI: http://dx.doi.org/10.1023/A:1021174726070 | - RAYMOND et al., "High-efficiency FLP and PHI03Y site-specific recombination in mammalian cells", PLOS ONE, (20070000), vol. 2, no. 1, doi:10.1371/journal.pone.0000162, page e162, XP055069825 DOI: http://dx.doi.org/10.1371/journal.pone.0000162 | - CARROLL, "A CRISPR approach to gene targeting", Molecular Therapy, (20120000), vol. 20, no. 9, doi:10.1038/mt.2012.171, pages 1658 - 60, XP055106489 DOI: http://dx.doi.org/10.1038/mt.2012.171 | - REISS et al., "RecA protein stimulates homologous recombination in plants", Proceedings of the National Academy of Sciences, (19960400), vol. 93, pages 3094 - 3098, XP002023622 DOI: http://dx.doi.org/10.1073/pnas.93.7.3094 | - ANDERS et al., "Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease", Nature, (20140900), vol. 513, pages 569 - 573, XP055240929 DOI: http://dx.doi.org/10.1038/nature13579 | - CHO SW et al., "Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease (includes Supplementary information)", Nat Biotechnol., (20130300), vol. 31, no. 3, pages 230 - 232,1-11, XP002699850 DOI: http://dx.doi.org/10.1038/nbt.2507 | - HWANG WY et al., "Efficient genome editing in zebrafish using a CRISPR-Cas system", Nat Biotechnol., (20130300), vol. 31, no. 3, pages 227 - 229, XP055540933 DOI: http://dx.doi.org/10.1038/nbt.2501 | - Melissa Pandika, "Jennifer Doudna, CRISPR Code Killer", (20140107), ZY, URL: http://www.ozy.com/risinq-stars/jennifer-doudna-crispr-code-killer/4690, XP055613817 | - Hwang et al., "Supplementary Material to: Efficient genome editing in zebrafish using a CRISPR-Cas system", Nature Biotechnology, pages 1 - 21, XP002718602 DOI: http://dx.doi.org/10.1038/nbt.2501 | - Robert Sanders, "Cheap and easy technique to snip DNA could revolutionize gene therapy", Berkeley News, URL: http://news.berkeley.edu/2013/01/07/cheap-and-easy-technique-to-snip-dna-could-revolutionize-gene-therapy/, XP055543406 | - "The CRISPR Revolution", CATALYST MAGAZINE, Berkeley, (20140709), URL: http://catalyst.berkeley.edu/slideshow/the-crisprrevolution/19/12/2014 12:40:53, XP055665429 | - VAN DER OOST, "New Tool for Genome Surgery", Science, (20130215), pages 768 - 770, XP055185006 DOI: http://dx.doi.org/10.1126/science.1234726 | - Gottesman, Susan, "Dicing defence in bacteria", Nature, (20110331), vol. 471, pages 588 - 589, XP055613828 DOI: http://dx.doi.org/10.1038/471588a | - Horvath et al., "RNA-guided genome editing à la carte", Cell Research, (20130601), pages 733 - 734, XP055184973 DOI: http://dx.doi.org/10.1038/cr.2013.39 | - RAN et al., "In vivo genome editing using Staphylococcus aureus Cas9", Nature, (20150000), vol. 520, pages 186 - 191, XP055206733 DOI: http://dx.doi.org/10.1038/nature14299 | - Keith Joung, "Building with Biological LEGO", BioTechniques,, (20120601), vol. 52, no. 6, page 351, XP055613839 DOI: http://dx.doi.org/10.2144/000113870 | - Davies et al., "Site Specific Mutation of the Zic2 Locus by Microinjection of TALEN mRNA in Mouse CD1, C3H and C57BL/6J Oocytes", PLoS ONE, (20130328), vol. 8, pages 1 - 7, XP055159248 DOI: http://dx.doi.org/10.1371/journal.pone.0060216 | - KIM et al., "In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni", Nature Communications, (20170000), vol. 8, pages 1 - 12, XP055435849 DOI: http://dx.doi.org/10.1038/ncomms14500 | - XU et al., "Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome", BMC Biotechnology, (20130000), vol. 13, pages 1 - 17, XP021171155 DOI: http://dx.doi.org/10.1186/1472-6750-13-87 | - ROBERTSON HD et al., "Purification and Properties of a Specific Escherichia coli Ribonuclease which Cleaves a Tyrosine Transfer Ribonucleic Acid Precursor", J Biol Chem., (19720825), vol. 247, no. 16, pages 5243 - 5251, XP055613873 | - GUERRIER-TAKADA C. et al., "The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme", Cell, (19831200), vol. 35, pages 849 - 857, XP023876209 DOI: http://dx.doi.org/10.1016/0092-8674(83)90117-4 | - MCCLAIN WH et al., "Model substrates for an RNA enzyme", Science, (19871023), vol. 238, no. 4826, pages 527 - 530, XP055613876 DOI: http://dx.doi.org/10.1126/science.2443980 | - FORSTER AC. et al., "External Guide Sequences for an RNA Enzyme", Science, (19900817), vol. 249, no. 4970, pages 783 - 786, XP055613881 DOI: http://dx.doi.org/10.1126/science.1697102 | - LI Y. et al., "Targeted cleavage of mRNA in vitro by RNase P from Escherichia coli (external guide sequence/model substrates)", Proc Natl Acad Sci U S A., (19920415), vol. 89, no. 8, pages 3185 - 3189, XP055613884 DOI: http://dx.doi.org/10.1073/pnas.89.8.3185 | - LIU F et al., "Inhibition of viral gene expression by the catalytic RNA subunlt o[ RNase P from Escherichia coli", Genes Dev., (19950215), vol. 9, no. 4, pages 471 - 480, XP055613887 DOI: http://dx.doi.org/10.1101/gad.9.4.471 | - PLEHN-DUJOWICH D. et al., "Effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease P", Proc Natl Acad Sci U S A., (19980623), vol. 95, no. 13, pages 7327 - 7332, XP002939541 DOI: http://dx.doi.org/10.1073/pnas.95.13.7327 | - KIM K et al., "Inhibition of gene expression in human cells using RNase P-derived ribozymes and external guide sequences", Biochimica et Biophysica Acta, (20070000), vol. 1769, pages 603 - 612, XP022349461 DOI: http://dx.doi.org/10.1016/j.bbaexp.2007.09.001 | - YUAN Y et al., "Selection of guide sequences that direct efficient cleavage of mRNA by human ribonuclease P", Science, (19940304), vol. 263, no. 5151, pages 1269 - 1273, XP002104825 DOI: http://dx.doi.org/10.1126/science.8122108 | - KILANI AF et al., "RNase P Ribozymes Selected in Vitro to Cleave a Viral mRNA Effectively Inhibit Its Expression in Cell Culture", J Biol Chem., (20000407), vol. 275, no. 14, pages 10611 - 10622, XP055613895 DOI: http://dx.doi.org/10.1074/jbc.275.14.10611 | - ZHOU T et al., "In Vitro Selection of External Guide Sequences for Directing RNase P-mediated Inhibition of Viral Gene Expression (includes Supplemental data)", J Biol Chem., (20020816), vol. 277, no. 33, pages 30112 - 30120,2-3, XP055613897 DOI: http://dx.doi.org/10.1074/jbc.M200183200 | - COX M M, "The FLP protein of the yeast 2-eum plasmid: Expression of a eukaryotic genetic recombination system in Escherichia coli", Proc Natl Acad Sci US A, (19830700), vol. 80, no. 14, pages 4223 - 4227, XP055613907 DOI: http://dx.doi.org/10.1073/pnas.80.14.4223 | - BABINEAU D. et al., "The FLP Protein of the 2-micron Plasmid of Yeast PURIFICATION OF THE PROTEIN FROM ESCHERICHIA COLI CELLS EXPRESSING THE CLONED FLP GENE", J Biol Chem., (19851005), vol. 260, no. 22, pages 12313 - 12319, XP055613910 | - O'GORMAN S. et al., "Recombinase-mediated gene activation and site-specific integration in mammalian cells", Science, (19910315), vol. 251, no. 4999, pages 1351 - 1355, XP002032986 DOI: http://dx.doi.org/10.1126/science.1900642 | - BUCHHOLZ F. et al., "Different Thermostabilities of FLP and Cre Recombinases: Implications for Applied Site-Specific Recombination", Nucleic Acids Res., (19961101), vol. 24, no. 21, pages 4256 - 4262, XP001004622 DOI: http://dx.doi.org/10.1093/nar/24.21.4256 | - BUCHHOLZ et al., "Improved properties of FLP recombinase evolved by cycling mutagenesis", Nature Biotechnology, (19980000), vol. 16, no. 7, pages 657 - 662, XP000775868 DOI: http://dx.doi.org/10.1038/nbt0798-657 | - RODRIGUEZ CI. et al., "High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP", Nat Genet., (20000600), vol. 25, no. 2, pages 139 - 140, XP003034016 DOI: http://dx.doi.org/10.1038/75973 | - LEENAY et al., "Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems", Molecular Cell, (20160000), vol. 62, pages 137 - 147, XP029496719 DOI: http://dx.doi.org/10.1016/j.molcel.2016.02.031 | - HSU et al., "DNA targeting specificity of RNA-guided Cas9 nucleases", Nature Biotechnology, (20130900), vol. 31, no. 9, pages 827 - 832, XP002718604 DOI: http://dx.doi.org/10.1038/nbt.2647 | - Ran et al., "Genome engineering using the CRISPR-Cas9 system", Nature Protocols, (20131101), vol. 8, no. 11, pages 2281 - 2308, XP002744123 DOI: http://dx.doi.org/10.1038/nprot.2013.143 | - DOENCH, J. G. et al., "Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9", Nature Biotech., (20160000), vol. 34, no. 2, pages 184 - 191, XP055551151 DOI: http://dx.doi.org/10.1038/nbt.3437 | - HOUSDEN, B. E. et al., "Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi", Science Signaling, (20150908), vol. 8, no. 393, doi:10.1126/scisignal.aab3729, pages 1 - 9, XP055665480 DOI: http://dx.doi.org/10.1126/scisignal.aab3729 | - REN, X. et al., "Enhanced Specificity and Efficiency of the CRISPR/Cas9 System with Optimized sgRNA Parameters in Drosophila", Cell Rep., (20140000), vol. 9, pages 1151 - 1162, XP055366968 DOI: http://dx.doi.org/10.1016/j.celrep.2014.09.044 | - "I GEM Learn About", iGEM, (20110000), Web Archive, URL: https://web.archive.org/web/20111008201737/ttps://igem.org | - "Project Introduction", IGEM 2011 Home Project, Arizona State University, (2011), URL: http://2011.igem.org/Team:Arizona_State/Project/Introduction, XP055665897 | - Anonymous, "Listeria innocua", IGEM 2001 Home Project, (2011), URL: http://2011.igem.org/Team:Arizona_State/Project/L_innocua, XP055665901 | - "Listeria Innocua", IGEM 2011 Home Project, (20110927), XP055665905 | - Jiaqiwu, "Wiki Freeze", (20111128), URL: https://asuigem.wordpress.com/2011/09/28/wiki-freeze/, XP055665910 | - STERNBERG et al., "DNA interrogation by the CRISPR RNA-guided endonuclease Cas9", Nature, (20140129), vol. 507, pages 62 - 67, XP055161285 DOI: http://dx.doi.org/10.1038/nature13011 | - NOZAWA T et al., "Crispr Inhibition of Prophage Acquisition in Streptococcus pyogenes", PLoS ONE, (20110000), vol. 6, no. 5, pages 1 - 10, XP055514497 DOI: http://dx.doi.org/10.1371/journal.pone.0019543 | - DINGERMANN, et al., "CRISPR/Cas9", Deutsche Apothekerzeitung, (20150705), no. 19, pages 47 - 51, XP055665920 | - SHAH et al., "Protospacer recognition motifs", RNA Biology, (20130500), vol. 10, no. 5, pages 891 - 899, XP055153088 DOI: http://dx.doi.org/10.4161/rna.23764 | - SHEN B et al., "Generation of gene-modified mice via Cas9/RNA-mediated gene targeting", Cell Research, (20130000), vol. 23, pages 720 - 723, XP055141533 DOI: http://dx.doi.org/10.1038/cr.2013.46 | - RHUN AL et al., "Small RNAs in stretococci", RNA Biology, (20120401), vol. 9, no. 4, pages 414 - 426, XP055665925 DOI: http://dx.doi.org/10.4161/rna.20104 | - BARRANGOU R et al., "CRISPR: New Horizons in Phage Resistance and Strain Identification", Annu. Rev. Food Sci. Technol., (20120000), vol. 3, pages 143 - 162, XP055378159 DOI: http://dx.doi.org/10.1146/annurev-food-022811-101134 | - YOUNG JC et al., "Phage-induced expression of CRISPR-associated proteins is revealed by shotgun proteomics in Streptococcus thermophilus.", PLoS One, (20120530), vol. 7, no. 5, pages 1 - 12, XP055665932 DOI: http://dx.doi.org/10.1371/journal.pone.0038077 | - "exogenous", Henderson's Dictionary of Biological Terms, (19950000), page 192, XP055666254 | - JINEK et al., "A programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity", Science, (20120000), vol. 337, doi:10.1126/science.1225829, pages 816 - 821, XP055549487 DOI: http://dx.doi.org/10.1126/science.1225829 | - FONFARA et al., "Phylogeny of Cas9 determines functional exchangeability of dual- RNA and Cas9 among orthologous type II CRISPR-Cas systems", Nucleic Acids Research, (20140000), vol. 42, doi:10.1093/nar/gkt1074, pages 2577 - 2590, XP055399937 DOI: http://dx.doi.org/10.1093/nar/gkt1074 | - LEENAY et al., "Identifying and Visualizing Functional PAM Diversity across CRISPR- Cas Systems", Mol. Cell, (20160000), vol. 62, pages 137 - 147, XP029496719 DOI: http://dx.doi.org/10.1016/j.molcel.2016.02.031 | - GASIUNAS et al., "Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria", PNAS, vol. 109, no. 39, doi:10.1073/pnas.1208507109, (20120900), pages E2579 - E2586, URL: www.pnas.org/cgi/doi/10.1073/pnas.1208507109, XP055569955 DOI: http://dx.doi.org/10.1073/pnas.1208507109 | - ENYEART et al., "Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis", Mob DNA 2014, (20140000), vol. 5, no. 1, doi:10.1186/1759-8753-5-2, page 2, XP021175117 DOI: http://dx.doi.org/10.1186/1759-8753-5-2 | - MINTON, "How can biochemical reactions within cells differ from those in test tubes?", J. Cell . Sci., (20060000), vol. 119, no. 14, pages 2863 - 2869+1pp, XP055464107 DOI: http://dx.doi.org/10.1242/jcs.03063 | - HALL et al., "Effects of inert volume-excluding macromolecules on protein fiber formation. I. Equilibrium models", Biophys. Chem., (20020000), vol. 98, pages 93 - 104, XP055464108 | - HALL et al., "Effects of inert volume-excluding macromolecules on protein fiber formation. II. Kinetic models for nucleated fiber growth", Biophys. Chem., (20040000), vol. 107, doi:10.1016/j.bpc.2003.09.016, pages 299 - 316, XP055464109 DOI: http://dx.doi.org/10.1016/j.bpc.2003.09.016 | - MARTIN, "Requirement for GroEL/GroES-Dependent Protein Folding under Nonpermissive Conditions of Macromolecular Crowding", Biochemistry, (20020000), vol. 41, doi:10.1021/bi015925l, pages 5050 - 5055, XP055464111 DOI: http://dx.doi.org/10.1021/bi015925l | - VAN DEN BERG et al., "Effects of macromolecular crowding on protein folding and aggregation", EMBO J., (19990000), vol. 18, no. 24, pages 6927 - 6933, XP055464113 | - Ran et al., "In vivo genome editing using Staphylococcus aureus Cas9 (Supplementary Information)", Nature, (20150401), vol. 520, no. 7546, pages 186 - 191, XP055304490 DOI: http://dx.doi.org/10.1038/nature14299 | - MOHR et al., "Rules for DNA target-site recognition by a lactococcal group II intron enable retargeting of the intron to specific DNA sequences", Genes & Development, (20000000), vol. 14, pages 559 - 573, XP055464117 | - GRYLLOS et al., "The CsrR/CsrS two-component system of group A Streptococcus responds to environmental Mg2+", PNAS, (20030000), vol. 100, no. 7, doi:10.1073/pnas.0636231100, pages 4227 - 4232, XP055464121 DOI: http://dx.doi.org/10.1073/pnas.0636231100 | - NEEF et al., "Deletion of a cation transporter promotes lysis in Streptococcus pneumoniae", Infection and immunity, (20110000), vol. 79, no. 6, doi:10.1128/IAI.00677-10, pages 2314 - 2323, XP055464123 DOI: http://dx.doi.org/10.1128/IAI.00677-10 | - LACASSE et al., "Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins", Nucleic Acids Research, (19950000), vol. 23, no. 10, doi:10.1093/nar/23.10.1647, pages 1647 - 56, XP055464125 DOI: http://dx.doi.org/10.1093/nar/23.10.1647 | - KIMCHI-SARFATY et al., "A'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity", Science, (20070000), vol. 315, pages 525 - 528, XP055464126 | - MAERTENS et al., "Gene optimization mechanisms: a multi- gene study reveals a high success rate of full-length human proteins expressed in Escherichia coli", Protein Sci., (20100000), vol. 19, doi:10.1002/pro.408, pages 1312 - 26, XP055441307 DOI: http://dx.doi.org/10.1002/pro.408 | - MAURO et al., "A critical analysis of codon optimization in human therapeutics", Trends Mol Med., (20140000), vol. 20, no. 11, doi:10.1016/j.molmed.2014.09.003, pages 604 - 613, XP055391316 DOI: http://dx.doi.org/10.1016/j.molmed.2014.09.003 | - AGUIRRE et al., "Genomic Copy Number Dictates a Gene -Independent Cell Response to CRISPR/Cas9 Targeting", Cancer Discovery, (20160000), vol. 6, doi:10.1158/2159-8290.CD-16-0154, pages 914 - 929, XP002795716 DOI: http://dx.doi.org/10.1158/2159-8290.CD-16-0154 | - IHRY et al., "P53 toxicity is a hurdle to CRISPR/CAS9 screening and engineering in human pluripotent stem cells", Nature Medicine, (20170000), pages 939 - 946, XP036542073 DOI: http://dx.doi.org/10.1038/s41591-018-0050-6 | - JIANG et al., "Successful transient expression of Cas9 and single guide RNA genes in Chlamydomonas reinhardtii", Eukaryot Cell, (20140000), vol. 13, doi:10.1128/EC.00213-14, pages 1465 - 9, XP055435460 DOI: http://dx.doi.org/10.1128/EC.00213-14 | - MASTROIANNI et al., "Group II Intron-Based Gene Targeting Reactions in Eukaryotes", PLoS One, (20080000), vol. 3, no. 9, pages 1 - 15, XP055149290 DOI: http://dx.doi.org/10.1371/journal.pone.0003121 | - JINEK et al., "RNA-programmed genome editing in human cells", eLife, (20130000), vol. 2, doi:10.7554/eLife.00471, page e00471, XP002699851 DOI: http://dx.doi.org/10.7554/eLife.00471 | - R SANDERS, "Cheap and easy technique to snip DNA could revolutionize gene therapy", Berkeley Press Release, (20130107), URL: http://news.berkeley.edu/ 2013/01/07 /cheap-and-easy-technique-to-snip-dna-could- revol ution ize- gene -thera py, XP055543406 | - CONG et al., "Multiplex Genome Engineering Using CRISPR/Cas Systems", Science, (20130000), vol. 339, doi:10.1126/science.1231143, pages 819 - 823, XP055458249 DOI: http://dx.doi.org/10.1126/science.1231143 | - MALI et al., "RNA-Guided Human Genome Engineering via Cas9", Science, (20130000), vol. 339, doi:10.1126/science.1232033, pages 823 - 826, XP055469277 DOI: http://dx.doi.org/10.1126/science.1232033 | - "The CRISPR Revolution", Catalyst Magazine, vol. 9, no. 1, (20140000), URL: http://catalyst.berkeley.edu/slideshow/the-crispr-revolution/, XP055665429 | - CARROLL, "A CRISPR Approach to Gene Targeting", Molecular Therapy, (20120000), vol. 20, no. 9, doi:10.1038/mt.2012.171, pages 1658 - 60, XP055106489 DOI: http://dx.doi.org/10.1038/mt.2012.171 | - BARRANGOU, "RNA-mediated programmable DNA cleavage", Nat. Biotechnol., (20120000), vol. 30, no. 9, doi:10.1038/nbt.2357, pages 836 - 838, XP055118675 DOI: http://dx.doi.org/10.1038/nbt.2357 | - ZAHID et al., "Protein Transduction Domains: Applications for Molecular Medicine", Curr. Gene Ther., (20120000), vol. 12, pages 374 - 380 | - Zahid et al., "Protein Transduction Domains: Applications for Molecular Medicine", Current Gene Therapy, (2012), vol. 12, pages 374 - 380, XP055666717 DOI: http://dx.doi.org/10.2174/156652312802762527 | - CORBI et al., "Chapter 9 Synthetic Zinc Finger Transcription Factors", CORBI et al., Shiro Iuchi, Zinc finger proteins: from atomic contact to cellular function, (20050000), pages 47 - 55, XP055344640 DOI: http://dx.doi.org/10.1007/0-387-27421-9_9 | - Nishimasu et al., "Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA, includes Supplemental Information)", Cell, (20140201), vol. 156, no. 5, pages 935 - 949,S1-S8, XP055423859 DOI: http://dx.doi.org/10.1016/j.cell.2014.02.001 | - JINEK, M et al., "A programmable Dual-RNA-Guided DNA Endonuclease in adaptive bacterial immunity", Science, (20120000), vol. 337, pages 816 - 821, XP055636516 DOI: http://dx.doi.org/10.1126/science.1225829 | - DELTCHEVA, E., "CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III", Nature, (20110000), vol. 471, doi:10.1038/nature09886, pages 602 - 607, XP055619637 DOI: http://dx.doi.org/10.1038/nature09886 | - SAPRANAUSKAS, R., "The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli", Nucleic Acids Research, (20110000), vol. 39, no. 21, doi:10.1093/nar/gkr606, page 9275 82, XP055265024 DOI: http://dx.doi.org/10.1093/nar/gkr606 | - CONG, L., "Multiplex Genome Engineering Using CRISPR Cas Systems", Science, (20130215), vol. 339, no. 6121, doi:10.1126/science.1231143, pages 819 - 23, XP055458249 DOI: http://dx.doi.org/10.1126/science.1231143 | - MALI, P., "RNA Guided Human Genome Engineering via Cas9", Science, (20130000), vol. 339, pages 823 - 826, XP055636507 DOI: http://dx.doi.org/10.1126/science.1232033 | - JINEK, M., "RNA-programmed genome editing in human cells", eLife, (20130000), vol. 2, pages 1 - 9, XP055245475 DOI: http://dx.doi.org/10.7554/eLife.00471 | - DOUDNA et al., "The new frontier of genome engineering with CRISPR-Cas9", Science, (20140000), vol. 346, no. 6213, doi:10.1126/science.1258096, XP055162699 DOI: http://dx.doi.org/10.1126/science.1258096 | - JIANG, F. et al., "CRISPR- Cas9 Structures and Mechanisms", Annu. Rev. Biophys., (20170000), vol. 46, pages 505 - 529, XP055362997 DOI: http://dx.doi.org/10.1146/annurev-biophys-062215-010822 | - ANDERS et al., "Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease", Nature, (20140925), vol. 513, no. 7519, doi:10.1038/nature13579, pages 569 - 573, XP055240929 DOI: http://dx.doi.org/10.1038/nature13579 | - PENG, R. et al., "Potential pitfalls of CRISPR/Cas9-mediated genome editing", FEBS Journal, (20160000), vol. 283, doi:10.1111/febs.13586, pages 1218 - 1231, XP055377561 DOI: http://dx.doi.org/10.1111/febs.13586 | - WANG, H. et al., "CRISPR/Cas9 in Genome Editing and Beyond", Annu. Rev. Biochem., (20160000), vol. 85, doi:10.1146/annurev-biochem-060815-014607, pages 227 - 64, XP055290311 DOI: http://dx.doi.org/10.1146/annurev-biochem-060815-014607 | - NISHIMASU et al., "Crystal structure of Cas9 in complex with Guide RNA and Target DNA", Cell, (20140000), vol. 156, no. 5, doi:10.1016/j.cell.2014.02.001, pages 935 - 949, XP028667665 DOI: http://dx.doi.org/10.1016/j.cell.2014.02.001 | - FONFARA et al., "Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-cas systems", Nucleic Acids Research, (20140000), vol. 42, no. 4, doi:10.1093/nar/gkt1074, pages 2577 - 2590, XP055399937 DOI: http://dx.doi.org/10.1093/nar/gkt1074 | - HWANG W.Y., "Efficient genome editing in zebrafish using a CRISPR-Cas system", Nat Biotechnol., (20130300), vol. 31, no. 3, doi:10.1038/nbt.2501, pages 227 - 9, XP055540926 DOI: http://dx.doi.org/10.1038/nbt.2501 | - GASIUNAS, G., "Cas9- crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria", proc. nat. acad. sci., (20120000), vol. 109, no. 39, doi:10.1073/pnas.1208507109, pages E2579 - E2586, XP055569955 DOI: http://dx.doi.org/10.1073/pnas.1208507109 | - RICHTER, C., "Function and Regulation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) / CRISPR Associated (Cas) Systems", Viruses, (20120000), vol. 4, doi:10.3390/v4102291, pages 2291 - 2311, XP055299758 DOI: http://dx.doi.org/10.3390/v4102291 | - MEI, YUE et al., "Recent Progress in CRISPR/Cas9 Technology", Genomics, (20160000), vol. 43, pages 63 - 72, XP029434259 DOI: http://dx.doi.org/10.1016/j.jgg.2016.01.001 | - CHO, S. W., "Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease", Nature Biotech., (20130000), vol. 31, no. 3, doi:10.1038/nbt.2507, XP002699850 DOI: http://dx.doi.org/10.1038/nbt.2507 | - DICARLO, J. E., "Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems", Nucleic Acids Research, (20130000), vol. 41, no. 7, doi:10.1093/nar/gkt135, page 4336 43, XP055604254 DOI: http://dx.doi.org/10.1093/nar/gkt135 | - JENNIFER DOUDNA, "The new frontier of genome engineering with CRISPR-Cas9", Catalyst Magazine, (20140709), pages 1 - 10, XP055162699 DOI: http://dx.doi.org/10.1126/science.1258096 | - MAKAROVA, K.S. et al., "An Updated Evolutionary Classification of CRISPR- Cas Systems", Nature, (20150000), vol. 13, doi:10.1038/nrmicro3569, pages 722 - 736, XP055271841 DOI: http://dx.doi.org/10.1038/nrmicro3569 | - KIM, E. et al., "In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni", Nat Communcations, (20170000), pages 1 - 122, XP055435850 DOI: http://dx.doi.org/10.1038/ncomms14500 | - CARROLL, D., "A CRISPR Approach to Gene Targeting", Molecular Therapy, (20120000), vol. 20, no. 9, doi:10.1038/mt.2012.171, pages 1658 - 1660, XP055106489 DOI: http://dx.doi.org/10.1038/mt.2012.171 | - BARRANGOU, R., "RNA-mediated programmable DNA cleavage", Nat. Biotechnology, (20120000), vol. 30, no. 9, doi:10.1038/nbt.2357, pages 836 - 838, XP055118675 DOI: http://dx.doi.org/10.1038/nbt.2357 | - FERRARI, A., "Kapitel 3", Gentechnish verändere Tiere in der Biomedizin, (20080000), pages 60 - 108, XP055671120 | - TAN W. et al., "Gene targeting, genome editing: from Dolly to editors", Transgenic Research, (20160000), pages 273 - 287, XP035933686 DOI: http://dx.doi.org/10.1007/s11248-016-9932-x | - Anonymous, "Vorschlag für eine Richtlinie des Europäischen Parlaments und des Rates über den rechtlichen Schutz biotechnologischer Erfindungen", Amtsblatt der Europäischen Gemeinschaften, (19961007), pages 1 - 9, XP055671122 | - THEN, CHRISTOPH, "Gentechnik, Patente und die Tierversuchsindustrie: Neue Gentechnik- Verfahren und Patente auf Säugetiere lassen die Zahl der Tierversuche weiter ansteigen", Test Biotech, (20160000), pages 1 - 27, XP055671126 |