IP Library › Granted Patent US 12,686,862
Granted Patent B2
US 12,686,862 · App. 17/246,466 · Granted Jul 21, 2026

CRISPR enzymes and systems

Inventors: Eugene Koonin (Bethesda, MD); Feng Zhang (Cambridge, MA); Yuri I. Wolf (Bethesda, MD); Sergey Shmakov (Moscow, RU); Konstantin Severinov (New Brunswick, NJ); Ekaterina Semenova (New Brunswick, NJ); Leonid Minakhin (New Brunswick, MD); Kira S. Makarova (Bethesda, MD); Silvana Konermann (Cambridge, MA); Julia Joung (Cambridge, MA); Jonathan S. Gootenberg (Cambridge, MA); Omar O. Abudayyeh (Cambridge, MA)
Assignees: The Broad Institute, Inc.; Massachusetts Institute of Technology; President and Fellows of Harvard College; Rutgers, the State University of New Jersey; Skolkovo Institute of Science and Technology; The United States of America, as represented by the Secretary, Department of Health and Human Services
C12N15/102A61K48/005C12N9/22C12N15/11C12N15/8213C12N2310/20C12N2800/80
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Quick Facts
Patent No.
US 12,686,862
App. No.
17/246,466
Filed
Apr 30, 2021
Granted
Jul 21, 2026
Kind
B2
Art Unit
1636
USPC
800/9
Abstract

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Claims (32)

1 . A composition comprising, a Type V Cas polypeptide that comprises a RuvC-like nuclease domain, a Zn finger region with at least one Zn-binding cysteine, but does not comprise an HNH domain, and one or more engineered nucleic acid components comprising a heterologous guide sequence that form a CRISPR-Cas complex with the Type V Cas polypeptide and that is capable of directing sequence-specific binding of said complex to a target sequence of a polynucleotide, wherein the heterologous guide sequence comprises a tracr sequence.

2 . The composition of claim 1 , that is capable of directing cleavage at the target sequence of the polynucleotide.

3 . The composition of claim 1 , wherein the one or more nucleic acid components are engineered to hybridize with a target sequence adjacent to a protospacer motif (PAM) in a genome of a eukaryotic cell.

4 . The composition of claim 1 , wherein the Cas polypeptide comprises one or more nuclear localization signals.

5 . The composition of claim 1 , wherein the one or more nucleic acid components comprise one or more modified nucleotides or one or more non-nucleotide moieties.

6 . The composition of claim 1 , wherein the composition comprises the formed CRISPR-Cas complex.

7 . The composition of claim 1 , wherein the composition comprises one or more vectors encoding the Cas polypeptide and the one or more nucleic acid components.

8 . The composition of claim 7 , wherein a polynucleotide sequence in the one or more vectors encoding the Cas polypeptide is codon optimized for expression in a eukaryotic cell.

9 . The composition of claim 7 , wherein the one or more vectors are viral vectors.

10 . The composition of claim 9 , wherein the one or more viral vectors are adenoviral vectors, lentiviral vectors, or adeno-associated viral vectors.

11 . The composition of claim 1 , wherein the composition comprises a mRNA encoding the Cas polypeptide.

12 . The composition of claim 11 , wherein the mRNA encoding the Cas polypeptide is comprised in a lipid nanoparticle, a liposome, an exosome, or a microvesicle.

13 . A method of targeting a polynucleotide, comprising contacting a sample comprising the polynucleotide with a CRISPR-Cas complex comprising, 1) a Type V Cas polypeptide comprising a RuvC nuclease domain, a Zn finger region with at least one Zn-binding cysteine, but not comprising a HNH domain, and 2) one or more nucleotide components comprising a heterologous guide sequence capable of directing sequence-specific binding of the CRISPR-Cas complex to a target sequence of the polynucleotide, wherein the heterologous guide sequence comprises a tracr sequence.

14 . The method of claim 13 , wherein the target sequence is in a eukaryotic cell.

15 . The method of claim 14 , wherein contacting the eukaryotic cell with the CRISPR-Cas complex results in modification of a gene or gene product, or modification in the expression of a gene product.

16 . A method of cleaving a polynucleotide, comprising contacting a sample comprising the polynucleotide with a CRISPR-Cas complex comprising, 1) a Type V Cas polypeptide comprising a RuvC nuclease domain, a Zn finger region with at least one Zn-binding cysteine, but not comprising a HNH domain, and 2) one or more nucleotide components comprising a heterologous guide sequence capable of directing sequence-specific cleavage with said complex at a target sequence of a polynucleotide, wherein the heterologous guide sequence comprises a tracr sequence.

17 . The method of claim 16 , wherein the target sequence is in a eukaryotic cell.

18 . The method of claim 17 , wherein contacting the eukaryotic cell with the CRISPR-Cas complex results in modification of a gene or gene product, or modification in the expression of a gene product.

19 . A composition comprising a Type V Cas polypeptide that comprises a RuvC-like nuclease domain, a Zn finger region with at least one Zn-binding cysteine, but does not comprise an HNH domain, and one or more engineered nucleic acid components comprising a heterologous guide sequence that form a complex with the Type V Cas polypeptide and that is capable of directing sequence-specific binding off said complex to a target sequence of a polynucleotide, wherein the Cas polypeptide comprises at least one mutation in the RuvC-like nuclease domain and is catalytically inactive, wherein the heterologous guide sequence comprises a tracr sequence.

20 . The composition of claim 19 , wherein the Cas polypeptide comprises one or more nuclear localization signals.

21 . The composition of claim 19 , wherein the Cas polypeptide is linked to a heterologous functional domain.

22 . The composition of claim 19 , wherein the one or more nucleic acid components comprise one or more modified nucleotides or one or more non-nucleotide moieties.

23 . The composition of claim 19 , wherein the composition comprises a formed CRISPR-Cas complex.

24 . The composition of claim 19 , wherein the composition comprises one or more vectors encoding the Cas polypeptide and the one or more nucleic acid components.

25 . The composition of claim 24 , wherein a polynucleotide sequence in the one or more vectors encoding the Cas polypeptide is codon optimized for expression in a eukaryotic cell.

26 . The composition of claim 24 , wherein the one or more vectors are viral vectors.

27 . The composition of claim 26 , wherein the one or more viral vectors are adenoviral vectors, lentiviral vectors, or adeno-associated viral vectors.

28 . The composition of claim 24 , wherein the composition comprises a mRNA encoding the Cas polypeptide.

29 . The composition of claim 28 , wherein the mRNA encoding the Cas polypeptide is comprised in a lipid nanoparticle, a liposome, an exosome, or a microvesicle.

30 . A method of targeting a polynucleotide, comprising contacting a sample comprising, 1) a catalytically inactive Type V Cas polypeptide linked to one or more heterologous functional domains, the Type V Cas polypeptide comprising a mutated RuvC-like nuclease domain, a Zn finger region with at least one Zn-binding cysteine, but does not comprise an HNH domain, and 2) one or more nucleic acid components comprising a heterologous guide sequence that form a CRISPR-Cas complex with the Type V Cas polypeptide and that is capable of directing sequence-specific binding of said complex to a target sequence of a polynucleotide, wherein the heterologous guide sequence comprises a tracr sequence.

31 . The method of claim 30 , wherein the target sequence is in a eukaryotic cell.

32 . The method of claim 31 , wherein contacting the eukaryotic cell with the CRISPR-Cas complex results in modification of a gene or gene product, or modification in expression of a gene product.

Assignments (11)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: ABUDAYYEH, OMAR O.
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 056126/0199 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: GOOTENBERG, JONATHAN
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 056126/0512 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: JOUNG, JULIA
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 056126/0670 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: KONERMANN, SILVANA
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 056126/0926 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: KOONIN, EUGENE
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 056127/0201 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: MAKAROVA, KIRA S.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 056127/0606 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: WOLF, YURI I.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 056127/0862 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: ZHANG, FENG
To: THE BROAD INSTITUTE, INC.; MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 056128/0212 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: SEMENOVA, EKATERINA; MINAKHIN, LEONID
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 056128/0758 →
PARTIAL ASSIGNMENT Recorded May 4, 2021
From: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
To: SKOLKOVO INSTITUTE OF SCIENCE AND TECHNOLOGY
Reel/Frame 056157/0652 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2021
From: SEVERINOV, KONSTANTIN
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 056177/0453 →
Continuity (5)
Continuation 15842073 · Dec 14, 2017
Continuation In Part PCTUS2016038238 · Jun 17, 2016
Provisional Application 62245264 · Oct 22, 2015
Provisional Application 62181663 · Jun 18, 2015
Related Publication 20210348157A1 · Nov 11, 2021
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