IP Library › Granted Patent US 12,281,338
Granted Patent B2
US 12,281,338 · App. 17/289,665 · Granted Apr 22, 2025

Nucleobase editors comprising GeoCas9 and uses thereof

Inventors: David R. Liu (Cambridge, MA); Yongjoo Kim (Cambridge, MA)
Assignees: The Broad Institute, Inc.; President and Fellows of Harvard College
C12N9/22C12N9/2497C12N9/78C12Y305/04004C12Y305/04005
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Quick Facts
Patent No.
US 12,281,338
App. No.
17/289,665
Granted
Apr 22, 2025
Kind
B2
Abstract

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids or the modification of nucleic acids or proteins, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins e.g., GeoCas9 or variants thereof, and effector domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing or protein modification are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a GeoCas9 and effector domains, are provided.

Claims (19)

1. A fusion protein comprising an amino acid sequence that is at least 85% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

2. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

3. A method comprising contacting a nucleic acid molecule with the fusion protein of claim 1 and a guide RNA, wherein the guide RNA comprises a sequence of at least 10 contiguous nucleotides that is complementary to a target sequence in the genome of an organism, and wherein the target sequence in the genome comprises a target base pair.

4. A complex comprising the fusion protein of claim 1 , and an RNA bound to the fusion protein.

5. A cell comprising the fusion protein of claim 1 .

6. A pharmaceutical composition comprising the fusion protein of claim 1 , and a pharmaceutically acceptable carrier.

7. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

8. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

9. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

10. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

11. The fusion protein of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 80-81.

12. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 80.

13. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 81.

14. A method comprising contacting a nucleic acid molecule with the complex of claim 4 .

15. The method of claim 14 , wherein the nucleic acid molecule comprises a target sequence associated with a disease or disorder.

16. The method of claim 14 , wherein the nucleic acid molecule comprises a point mutation associated with a disease or disorder.

17. The method of claim 16 , wherein the activity of the fusion protein results in a correction of the point mutation.

18. The method of claim 14 , wherein the contacting is performed in vivo in a subject.

19. The method of claim 14 , wherein the contacting is performing in vitro.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: HOWARD HUGHES MEDICAL INSTITUTE
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 059613/0487 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: KIM, YONGJOO
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 059613/0528 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
To: THE BROAD INSTITUTE, INC.
Reel/Frame 059613/0536 →
CONFIRMATION OF ASSIGNMENT Recorded Apr 15, 2022
From: LIU, DAVID R.
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 059722/0881 →
Continuity (2)
Provisional Application 62752225 · Oct 29, 2018
Related Publication 20220389395A1 · Dec 8, 2022
References Cited (400)
US 4182449A · Kozlow · 1980 [cited by applicant]
US 4186183A · Steck et al. · 1980 [cited by applicant]
US 4217344A · Vanlerberghe et al. · 1980 [cited by applicant]
US 4235871A · Papahadjopoulos et al. · 1980 [cited by applicant]
US 4261975A · Fullerton et al. · 1981 [cited by applicant]
US 4485054A · Mezei et al. · 1984 [cited by applicant]
US 4501728A · Geho et al. · 1985 [cited by applicant]
US 4663290A · Weis et al. · 1987 [cited by applicant]
US 4737323A · Martin et al. · 1988 [cited by applicant]
US 4774085A · Fidler · 1988 [cited by applicant]
US 4797368A · Carter et al. · 1989 [cited by applicant]
US 4837028A · Allen · 1989 [cited by applicant]
US 4873316A · Meade et al. · 1989 [cited by applicant]
US 4880635A · Janoff et al. · 1989 [cited by applicant]
US 4889818A · Gelfand et al. · 1989 [cited by applicant]
US 4897355A · Eppstein et al. · 1990 [cited by applicant]
US 4906477A · Kurono et al. · 1990 [cited by applicant]
US 4911928A · Wallach · 1990 [cited by applicant]
US 4917951A · Wallach · 1990 [cited by applicant]
US 4920016A · Allen et al. · 1990 [cited by applicant]
US 4921757A · Wheatley et al. · 1990 [cited by applicant]
US 4946787A · Eppstein et al. · 1990 [cited by applicant]
US 4965185A · Grischenko et al. · 1990 [cited by applicant]
US 5017492A · Kotewicz et al. · 1991 [cited by applicant]
US 5047342A · Chatterjee · 1991 [cited by applicant]
US 5049386A · Eppstein et al. · 1991 [cited by applicant]
US 5079352A · Gelfand et al. · 1992 [cited by applicant]
US 5139941A · Muzyczka et al. · 1992 [cited by applicant]
US 5173414A · Lebkowski et al. · 1992 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5244797A · Kotewicz et al. · 1993 [cited by applicant]
US 5270179A · Chatterjee · 1993 [cited by applicant]
US 5374553A · Gelfand et al. · 1994 [cited by applicant]
US 5405776A · Kotewicz et al. · 1995 [cited by applicant]
US 5436149A · Barnes · 1995 [cited by applicant]
US 5449639A · Wei et al. · 1995 [cited by applicant]
US 5496714A · Comb et al. · 1996 [cited by applicant]
US 5512462A · Cheng · 1996 [cited by applicant]
US 5580737A · Polisky et al. · 1996 [cited by applicant]
US 5614365A · Tabor et al. · 1997 [cited by applicant]
US 5652094A · Usman et al. · 1997 [cited by applicant]
US 5658727A · Barbas et al. · 1997 [cited by applicant]
US 5668005A · Kotewicz et al. · 1997 [cited by applicant]
US 5677152A · Birch et al. · 1997 [cited by applicant]
US 5767099A · Harris et al. · 1998 [cited by applicant]
US 5780053A · Ashley et al. · 1998 [cited by applicant]
US 5830430A · Unger et al. · 1998 [cited by applicant]
US 5834247A · Comb et al. · 1998 [cited by applicant]
US 5835699A · Kimura · 1998 [cited by applicant]
US 5844075A · Kawakami et al. · 1998 [cited by applicant]
US 5849548A · Haseloff et al. · 1998 [cited by applicant]
US 5851548A · Dattagupta et al. · 1998 [cited by applicant]
US 5855910A · Ashley et al. · 1999 [cited by applicant]
US 5856463A · Blankenborg et al. · 1999 [cited by applicant]
US 5962313A · Podsakoff et al. · 1999 [cited by applicant]
US 5981182A · Jacobs, Jr. et al. · 1999 [cited by applicant]
US 6015794A · Haseloff et al. · 2000 [cited by applicant]
US 6057153A · George et al. · 2000 [cited by applicant]
US 6063608A · Kotewicz et al. · 2000 [cited by applicant]
US 6077705A · Duan et al. · 2000 [cited by applicant]
US 6156509A · Schellenberger · 2000 [cited by applicant]
US 6183998B1 · Ivanov et al. · 2001 [cited by applicant]
US 6355415B1 · Wagner et al. · 2002 [cited by applicant]
US 6429298B1 · Ellington et al. · 2002 [cited by applicant]
US 6453242B1 · Eisenberg et al. · 2002 [cited by applicant]
US 6479264B1 · Louwrier · 2002 [cited by applicant]
US 6503717B2 · Case et al. · 2003 [cited by applicant]
US 6534261B1 · Cox, III et al. · 2003 [cited by applicant]
US 6558671B1 · Slingluff et al. · 2003 [cited by applicant]
US 6589768B1 · Kotewicz et al. · 2003 [cited by applicant]
US 6599692B1 · Case et al. · 2003 [cited by applicant]
US 6607882B1 · Cox, III et al. · 2003 [cited by applicant]
US 6610522B1 · Kotewicz et al. · 2003 [cited by applicant]
US 6689558B2 · Case · 2004 [cited by applicant]
US 6716973B2 · Baskerville et al. · 2004 [cited by applicant]
US 6824978B1 · Cox, III et al. · 2004 [cited by applicant]
US 6933113B2 · Case et al. · 2005 [cited by applicant]
US 6979539B2 · Cox, III et al. · 2005 [cited by applicant]
US 7013219B2 · Case et al. · 2006 [cited by applicant]
US 7045337B2 · Schultz et al. · 2006 [cited by applicant]
US 7067650B1 · Tanaka · 2006 [cited by applicant]
US 7070928B2 · Liu et al. · 2006 [cited by applicant]
US 7078208B2 · Smith et al. · 2006 [cited by applicant]
US 7083970B2 · Schultz et al. · 2006 [cited by applicant]
US 7163824B2 · Cox, III et al. · 2007 [cited by applicant]
US 7192739B2 · Liu et al. · 2007 [cited by applicant]
US 7223545B2 · Liu et al. · 2007 [cited by applicant]
US 7354761B2 · Schultz et al. · 2008 [cited by applicant]
US 7368275B2 · Schultz et al. · 2008 [cited by applicant]
US 7419669B2 · Kosmatopoulos et al. · 2008 [cited by applicant]
US 7442160B2 · Liu et al. · 2008 [cited by applicant]
US 7476500B1 · Liu et al. · 2009 [cited by applicant]
US 7476734B2 · Liu · 2009 [cited by applicant]
US 7479573B2 · Chu et al. · 2009 [cited by applicant]
US 7488718B2 · Scheinberg et al. · 2009 [cited by applicant]
US 7491494B2 · Liu et al. · 2009 [cited by applicant]
US 7541450B2 · Liu et al. · 2009 [cited by applicant]
US 7557068B2 · Liu et al. · 2009 [cited by applicant]
US 7595179B2 · Chen et al. · 2009 [cited by applicant]
US 7638300B2 · Schultz et al. · 2009 [cited by applicant]
US 7670807B2 · Lampson et al. · 2010 [cited by applicant]
US 7678554B2 · Liu et al. · 2010 [cited by applicant]
US 7713721B2 · Schultz et al. · 2010 [cited by applicant]
US 7771935B2 · Liu et al. · 2010 [cited by applicant]
US 7794931B2 · Breaker et al. · 2010 [cited by applicant]
US 7807408B2 · Liu et al. · 2010 [cited by applicant]
US 7851658B2 · Liu et al. · 2010 [cited by applicant]
US 7915025B2 · Schultz et al. · 2011 [cited by applicant]
US 7919277B2 · Russell et al. · 2011 [cited by applicant]
US 7993672B2 · Huang et al. · 2011 [cited by applicant]
US 7998904B2 · Liu et al. · 2011 [cited by applicant]
US 7999071B2 · Schlom et al. · 2011 [cited by applicant]
US 8012739B2 · Schultz et al. · 2011 [cited by applicant]
US 8017323B2 · Liu et al. · 2011 [cited by applicant]
US 8017755B2 · Liu et al. · 2011 [cited by applicant]
US 8030074B2 · Schultz et al. · 2011 [cited by applicant]
US 8067556B2 · Hogrefe et al. · 2011 [cited by applicant]
US 8114648B2 · Schultz et al. · 2012 [cited by applicant]
US 8173364B2 · Schultz et al. · 2012 [cited by applicant]
US 8173392B2 · Schultz et al. · 2012 [cited by applicant]
US 8183012B2 · Schultz et al. · 2012 [cited by applicant]
US 8183178B2 · Liu et al. · 2012 [cited by applicant]
US 8206914B2 · Liu et al. · 2012 [cited by applicant]
US 8354380B2 · Liu et al. · 2013 [cited by applicant]
US 8361725B2 · Russell et al. · 2013 [cited by applicant]
US 8394604B2 · Liu et al. · 2013 [cited by applicant]
US 8440431B2 · Voytas et al. · 2013 [cited by applicant]
US 8440432B2 · Voytas et al. · 2013 [cited by applicant]
US 8450471B2 · Voytas et al. · 2013 [cited by applicant]
US 8492082B2 · De Franciscis et al. · 2013 [cited by applicant]
US 8546553B2 · Terns et al. · 2013 [cited by applicant]
US 8569256B2 · Heyes et al. · 2013 [cited by applicant]
US 8586363B2 · Voytas et al. · 2013 [cited by applicant]
US 8680069B2 · de Fougerolles et al. · 2014 [cited by applicant]
US 8691729B2 · Liu et al. · 2014 [cited by applicant]
US 8691750B2 · Constien et al. · 2014 [cited by applicant]
US 8697359B1 · Zhang · 2014 [cited by applicant]
US 8697439B2 · Mangeot et al. · 2014 [cited by applicant]
US 8697853B2 · Voytas et al. · 2014 [cited by applicant]
US 8709466B2 · Coady et al. · 2014 [cited by applicant]
US 8728526B2 · Heller · 2014 [cited by applicant]
US 8748667B2 · Budzik et al. · 2014 [cited by applicant]
US 8758810B2 · Okada et al. · 2014 [cited by applicant]
US 8759103B2 · Kim et al. · 2014 [cited by applicant]
US 8759104B2 · Unciti-Broceta et al. · 2014 [cited by applicant]
US 8771728B2 · Huang et al. · 2014 [cited by applicant]
US 8790664B2 · Pitard et al. · 2014 [cited by applicant]
US 8795965B2 · Zhang · 2014 [cited by applicant]
US 8822663B2 · Schrum et al. · 2014 [cited by applicant]
US 8835148B2 · Janulaitis et al. · 2014 [cited by applicant]
US 8846578B2 · McCray et al. · 2014 [cited by applicant]
US 8871445B2 · Cong et al. · 2014 [cited by applicant]
US 8889418B2 · Zhang et al. · 2014 [cited by applicant]
US 8900814B2 · Yasukawa et al. · 2014 [cited by applicant]
US 8945839B2 · Zhang · 2015 [cited by applicant]
US 8975232B2 · Liu et al. · 2015 [cited by applicant]
US 8993233B2 · Zhang et al. · 2015 [cited by applicant]
US 8999641B2 · Zhang et al. · 2015 [cited by applicant]
US 9023594B2 · Liu et al. · 2015 [cited by applicant]
US 9023649B2 · Mali et al. · 2015 [cited by applicant]
US 9034650B2 · Padidam · 2015 [cited by applicant]
US 9068179B1 · Liu et al. · 2015 [cited by applicant]
US 9150626B2 · Liu et al. · 2015 [cited by applicant]
US 9163271B2 · Schultz et al. · 2015 [cited by applicant]
US 9163284B2 · Liu et al. · 2015 [cited by applicant]
US 9181535B2 · Liu et al. · 2015 [cited by applicant]
US 9200045B2 · Liu et al. · 2015 [cited by applicant]
US 9221886B2 · Liu et al. · 2015 [cited by applicant]
US 9228207B2 · Liu et al. · 2016 [cited by applicant]
US 9234213B2 · Wu · 2016 [cited by applicant]
US 9243038B2 · Liu et al. · 2016 [cited by applicant]
US 9267127B2 · Liu et al. · 2016 [cited by applicant]
US 9322006B2 · Liu et al. · 2016 [cited by applicant]
US 9322037B2 · Liu et al. · 2016 [cited by applicant]
US 9340799B2 · Liu et al. · 2016 [cited by applicant]
US 9340800B2 · Liu et al. · 2016 [cited by applicant]
US 9359599B2 · Liu et al. · 2016 [cited by applicant]
US 9388430B2 · Liu et al. · 2016 [cited by applicant]
US 9394537B2 · Liu et al. · 2016 [cited by applicant]
US 9434774B2 · Liu et al. · 2016 [cited by applicant]
US 9458484B2 · Ma et al. · 2016 [cited by applicant]
US 9512446B1 · Joung et al. · 2016 [cited by applicant]
US 9526724B2 · Oshlack et al. · 2016 [cited by applicant]
US 9526784B2 · Liu et al. · 2016 [cited by applicant]
US 9534210B2 · Park et al. · 2017 [cited by applicant]
US 9580698B1 · Xu et al. · 2017 [cited by applicant]
US 9610322B2 · Liu et al. · 2017 [cited by applicant]
US 9637739B2 · Siksnys et al. · 2017 [cited by applicant]
US 9663770B2 · Rogers et al. · 2017 [cited by applicant]
US 9695446B2 · Mangeot et al. · 2017 [cited by applicant]
US 9737604B2 · Liu et al. · 2017 [cited by applicant]
US 9738693B2 · Telford et al. · 2017 [cited by applicant]
US 9753340B2 · Saitou · 2017 [cited by applicant]
US 9771574B2 · Liu et al. · 2017 [cited by applicant]
US 9783791B2 · Hogrefe et al. · 2017 [cited by applicant]
US 9816093B1 · Donohoue et al. · 2017 [cited by applicant]
US 9840538B2 · Telford et al. · 2017 [cited by applicant]
US 9840690B2 · Karli et al. · 2017 [cited by applicant]
US 9840699B2 · Liu et al. · 2017 [cited by applicant]
US 9840702B2 · Collingwood et al. · 2017 [cited by applicant]
US 9850521B2 · Braman et al. · 2017 [cited by applicant]
US 9873907B2 · Zeiner et al. · 2018 [cited by applicant]
US 9879270B2 · Hittinger et al. · 2018 [cited by applicant]
US 9914939B2 · Church et al. · 2018 [cited by applicant]
US 9932567B1 · Xu et al. · 2018 [cited by applicant]
US 9938288B1 · Kishi et al. · 2018 [cited by applicant]
US 9944933B2 · Storici et al. · 2018 [cited by applicant]
US 9982279B1 · Gill et al. · 2018 [cited by applicant]
US 9999671B2 · Liu et al. · 2018 [cited by applicant]
US 10011868B2 · Liu et al. · 2018 [cited by applicant]
US 10053725B2 · Liu et al. · 2018 [cited by applicant]
US 10059940B2 · Zhong · 2018 [cited by applicant]
US 10077453B2 · Liu et al. · 2018 [cited by applicant]
US 10113163B2 · Liu et al. · 2018 [cited by applicant]
US 10150955B2 · Lambowitz et al. · 2018 [cited by applicant]
US 10167457B2 · Liu et al. · 2019 [cited by applicant]
US 10179911B2 · Liu et al. · 2019 [cited by applicant]
US 10189831B2 · Arrington et al. · 2019 [cited by applicant]
US 10202593B2 · Liu et al. · 2019 [cited by applicant]
US 10202658B2 · Parkin et al. · 2019 [cited by applicant]
US 10227581B2 · Liu et al. · 2019 [cited by applicant]
US 10323236B2 · Liu et al. · 2019 [cited by applicant]
US 10336997B2 · Liu et al. · 2019 [cited by applicant]
US 10358670B2 · Janulaitis et al. · 2019 [cited by applicant]
US 10392674B2 · Liu et al. · 2019 [cited by applicant]
US 10407474B2 · Liu et al. · 2019 [cited by applicant]
US 10407697B2 · Doudna et al. · 2019 [cited by applicant]
US 10465176B2 · Liu et al. · 2019 [cited by applicant]
US 10508298B2 · Liu et al. · 2019 [cited by applicant]
US 10583201B2 · Chen et al. · 2020 [cited by applicant]
US 10597679B2 · Liu et al. · 2020 [cited by applicant]
US 10612011B2 · Liu et al. · 2020 [cited by applicant]
US 10640767B2 · Maianti et al. · 2020 [cited by applicant]
US 10682410B2 · Liu et al. · 2020 [cited by applicant]
US 10704062B2 · Liu et al. · 2020 [cited by applicant]
US 10745677B2 · Maianti et al. · 2020 [cited by applicant]
US 10858639B2 · Liu et al. · 2020 [cited by applicant]
US 10912833B2 · Liu et al. · 2021 [cited by applicant]
US 10930367B2 · Zhang et al. · 2021 [cited by applicant]
US 10947530B2 · Liu et al. · 2021 [cited by applicant]
US 10954548B2 · Liu et al. · 2021 [cited by applicant]
US 10968253B2 · Ohlmann et al. · 2021 [cited by applicant]
US 11046948B2 · Liu et al. · 2021 [cited by applicant]
US 11053481B2 · Liu et al. · 2021 [cited by applicant]
US 11078429B2 · Liu et al. · 2021 [cited by applicant]
US 11124782B2 · Liu et al. · 2021 [cited by applicant]
US 11214780B2 · Liu et al. · 2022 [cited by applicant]
US 11268082B2 · Liu et al. · 2022 [cited by applicant]
US 11299755B2 · Liu et al. · 2022 [cited by applicant]
US 11306324B2 · Liu et al. · 2022 [cited by applicant]
US 11319532B2 · Liu et al. · 2022 [cited by applicant]
US 11421016B2 · Nguyen et al. · 2022 [cited by applicant]
US 11447770B1 · Liu et al. · 2022 [cited by applicant]
US 11542496B2 · Liu et al. · 2023 [cited by applicant]
US 11542509B2 · Maianti et al. · 2023 [cited by applicant]
US 11560566B2 · Liu et al. · 2023 [cited by applicant]
US 11578343B2 · Liu et al. · 2023 [cited by applicant]
US 11643652B2 · Liu et al. · 2023 [cited by applicant]
US 11661590B2 · Liu et al. · 2023 [cited by applicant]
US 11692184B2 · Kyrpides · 2023 [cited by examiner]
US 11702651B2 · Liu et al. · 2023 [cited by applicant]
US 11732274B2 · Liu et al. · 2023 [cited by applicant]
US 11795443B2 · Liu et al. · 2023 [cited by applicant]
US 11795452B2 · Liu et al. · 2023 [cited by applicant]
US 11820969B2 · Maianti et al. · 2023 [cited by applicant]
US 11898179B2 · Maianti et al. · 2024 [cited by applicant]
US 11912985B2 · Liu et al. · 2024 [cited by applicant]
US 11920181B2 · Liu et al. · 2024 [cited by applicant]
US 11932884B2 · Liu et al. · 2024 [cited by applicant]
US 11999947B2 · Liu et al. · 2024 [cited by applicant]
US 12006520B2 · Liu et al. · 2024 [cited by applicant]
US 12031126B2 · Liu et al. · 2024 [cited by applicant]
US 12043852B2 · Liu et al. · 2024 [cited by applicant]
US 20030082575A1 · Schultz et al. · 2003 [cited by applicant]
US 20030087817A1 · Cox et al. · 2003 [cited by applicant]
US 20030096337A1 · Hillman et al. · 2003 [cited by applicant]
US 20030108885A1 · Schultz et al. · 2003 [cited by applicant]
US 20030119764A1 · Loeb et al. · 2003 [cited by applicant]
US 20030167533A1 · Yadav et al. · 2003 [cited by applicant]
US 20030203480A1 · Kovesdi et al. · 2003 [cited by applicant]
US 20040003420A1 · Kuhn et al. · 2004 [cited by applicant]
US 20040115184A1 · Smith et al. · 2004 [cited by applicant]
US 20040156861A1 · Figdor et al. · 2004 [cited by applicant]
US 20040197892A1 · Moore et al. · 2004 [cited by applicant]
US 20040203109A1 · Lal et al. · 2004 [cited by applicant]
US 20050136429A1 · Guarente et al. · 2005 [cited by applicant]
US 20050222030A1 · Allison · 2005 [cited by applicant]
US 20050260626A1 · Lorens et al. · 2005 [cited by applicant]
US 20060088864A1 · Smolke et al. · 2006 [cited by applicant]
US 20060104984A1 · Littlefield et al. · 2006 [cited by applicant]
US 20060246568A1 · Honjo et al. · 2006 [cited by applicant]
US 20070015238A1 · Snyder et al. · 2007 [cited by applicant]
US 20070049533A1 · Liu et al. · 2007 [cited by applicant]
US 20070264692A1 · Liu et al. · 2007 [cited by applicant]
US 20070269817A1 · Shapero · 2007 [cited by applicant]
US 20080008697A1 · Mintier et al. · 2008 [cited by applicant]
US 20080051317A1 · Church et al. · 2008 [cited by applicant]
US 20080124725A1 · Barrangou et al. · 2008 [cited by applicant]
US 20080182254A1 · Hall et al. · 2008 [cited by applicant]
US 20080220502A1 · Schellenberger et al. · 2008 [cited by applicant]
US 20080241917A1 · Akita et al. · 2008 [cited by applicant]
US 20080268516A1 · Perreault et al. · 2008 [cited by applicant]
US 20090111119A1 · Doyon et al. · 2009 [cited by applicant]
US 20090130718A1 · Short · 2009 [cited by applicant]
US 20090215878A1 · Tan et al. · 2009 [cited by applicant]
US 20090234109A1 · Han et al. · 2009 [cited by applicant]
US 20100076057A1 · Sontheimer et al. · 2010 [cited by applicant]
US 20100093617A1 · Barrangou et al. · 2010 [cited by applicant]
US 20100104690A1 · Barrangou et al. · 2010 [cited by applicant]
US 20100273857A1 · Thakker et al. · 2010 [cited by applicant]
US 20100305197A1 · Che · 2010 [cited by applicant]
US 20100316643A1 · Eckert et al. · 2010 [cited by applicant]
US 20110016540A1 · Weinstein et al. · 2011 [cited by applicant]
US 20110059160A1 · Essner et al. · 2011 [cited by applicant]
US 20110059502A1 · Chalasani · 2011 [cited by applicant]
US 20110104787A1 · Church et al. · 2011 [cited by applicant]
US 20110177495A1 · Liu et al. · 2011 [cited by applicant]
US 20110189775A1 · Ainley et al. · 2011 [cited by applicant]
US 20110189776A1 · Terns et al. · 2011 [cited by applicant]
US 20110217739A1 · Terns et al. · 2011 [cited by applicant]
US 20110301073A1 · Gregory et al. · 2011 [cited by applicant]
US 20120129759A1 · Liu et al. · 2012 [cited by applicant]
US 20120141523A1 · Castado et al. · 2012 [cited by applicant]
US 20120244601A1 · Bertozzi et al. · 2012 [cited by applicant]
US 20120270273A1 · Zhang et al. · 2012 [cited by applicant]
US 20120322861A1 · Byrne et al. · 2012 [cited by applicant]
US 20130022980A1 · Nelson et al. · 2013 [cited by applicant]
US 20130059931A1 · Petersen-Mahrt et al. · 2013 [cited by applicant]
US 20130108657A1 · Yee et al. · 2013 [cited by applicant]
US 20130117869A1 · Duchateau et al. · 2013 [cited by applicant]
US 20130130248A1 · Haurwitz et al. · 2013 [cited by applicant]
US 20130158245A1 · Russell et al. · 2013 [cited by applicant]
US 20130165389A1 · Schellenberger et al. · 2013 [cited by applicant]
US 20130212725A1 · Kuhn et al. · 2013 [cited by applicant]
US 20130309720A1 · Schultz et al. · 2013 [cited by applicant]
US 20130344117A1 · Mirosevich et al. · 2013 [cited by applicant]
US 20130345064A1 · Liu et al. · 2013 [cited by applicant]
US 20140004280A1 · Loomis · 2014 [cited by applicant]
US 20140005269A1 · Ngwuluka et al. · 2014 [cited by applicant]
US 20140017214A1 · Cost · 2014 [cited by applicant]
US 20140018404A1 · Chen et al. · 2014 [cited by applicant]
US 20140039692A1 · Leen et al. · 2014 [cited by applicant]
US 20140044793A1 · Goll et al. · 2014 [cited by applicant]
US 20140065711A1 · Liu et al. · 2014 [cited by applicant]
US 20140068797A1 · Doudna et al. · 2014 [cited by applicant]
US 20140127752A1 · Zhou et al. · 2014 [cited by applicant]
US 20140128449A1 · Liu et al. · 2014 [cited by applicant]
US 20140141094A1 · Smyth et al. · 2014 [cited by applicant]
US 20140141487A1 · Feldman et al. · 2014 [cited by applicant]
US 20140153118A1 · Onozaki · 2014 [cited by applicant]
US 20140179770A1 · Zhang et al. · 2014 [cited by applicant]
US 20140186843A1 · Zhang et al. · 2014 [cited by applicant]
US 20140186919A1 · Zhang et al. · 2014 [cited by applicant]
US 20140186958A1 · Zhang et al. · 2014 [cited by applicant]
US 20140201858A1 · Ostertag et al. · 2014 [cited by applicant]
US 20140234289A1 · Liu et al. · 2014 [cited by applicant]
US 20140248702A1 · Zhang et al. · 2014 [cited by applicant]
US 20140273037A1 · Wu · 2014 [cited by applicant]
US 20140273226A1 · Wu · 2014 [cited by applicant]
US 20140273230A1 · Chen et al. · 2014 [cited by applicant]
US 20140273234A1 · Zhang et al. · 2014 [cited by applicant]
US 20140283156A1 · Zador et al. · 2014 [cited by applicant]
US 20140295556A1 · Joung et al. · 2014 [cited by applicant]
US 20140295557A1 · Joung et al. · 2014 [cited by applicant]
US 20140342456A1 · Mali et al. · 2014 [cited by applicant]
US 20140342457A1 · Mali et al. · 2014 [cited by applicant]
US 20140342458A1 · Mali et al. · 2014 [cited by applicant]
US 20140349400A1 · Jakimo et al. · 2014 [cited by applicant]
US 20140356867A1 · Peter et al. · 2014 [cited by applicant]
US 20140356956A1 · Church et al. · 2014 [cited by applicant]
US 20140356958A1 · Mali et al. · 2014 [cited by applicant]
US 20140356959A1 · Church et al. · 2014 [cited by applicant]
US 20140357523A1 · Zeiner et al. · 2014 [cited by applicant]
US 20140377868A1 · Joung et al. · 2014 [cited by applicant]
US 20150010526A1 · Liu et al. · 2015 [cited by applicant]
US 20150031089A1 · Lindstrom · 2015 [cited by applicant]
US 20150031132A1 · Church et al. · 2015 [cited by applicant]
US 20150031133A1 · Church et al. · 2015 [cited by applicant]
US 20150044191A1 · Liu et al. · 2015 [cited by applicant]
US 20150044192A1 · Liu et al. · 2015 [cited by applicant]
US 20150044772A1 · Zhao · 2015 [cited by applicant]
US 20150050699A1 · Siksnys et al. · 2015 [cited by applicant]
US 20150056177A1 · Liu et al. · 2015 [cited by applicant]
US 20150056629A1 · Guthrie-Honea · 2015 [cited by applicant]
US 20150064138A1 · Lu et al. · 2015 [cited by applicant]
US 20150064789A1 · Paschon et al. · 2015 [cited by applicant]
US 20150071898A1 · Liu et al. · 2015 [cited by applicant]
US 20150071899A1 · Liu et al. · 2015 [cited by applicant]
US 20150071900A1 · Liu et al. · 2015 [cited by applicant]
US 20150071901A1 · Liu et al. · 2015 [cited by applicant]
US 20150071902A1 · Liu et al. · 2015 [cited by applicant]
US 20150071903A1 · Liu et al. · 2015 [cited by applicant]
US 20150071906A1 · Liu et al. · 2015 [cited by applicant]
US 20150079680A1 · Bradley et al. · 2015 [cited by applicant]
US 20150079681A1 · Zhang · 2015 [cited by applicant]
US 20150098954A1 · Hyde et al. · 2015 [cited by applicant]
US 20150118216A1 · Liu et al. · 2015 [cited by applicant]
US 20150128300A1 · Warming et al. · 2015 [cited by applicant]
US 20150132269A1 · Orkin et al. · 2015 [cited by applicant]
US 20150140664A1 · Byrne et al. · 2015 [cited by applicant]
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