Engineered type ii cas polynucleotides with reduced immunogenicity and uses thereof
AssigneesThe Broad Institute, Inc., Massachusetts Institute of Technology, Cyrus Biotechnology, Inc.
InventorsFeng Zhang, Rumya Raghavan, Rhiannon Macrae, Yifan Song, Lucas Nivon, Indigo King
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Abstract
Engineered Type II Cas polypeptides with reduced immunogenicity, CRISPR-Cas systems thereof, compositions thereof, delivery systems thereof, and methods of use thereof for modifying target polynucleotides, such as, for example, in cells.
Claims24
An engineered Type II Cas comprising one or more amino acid substitutions in one or more epitopes corresponding to one or more MHC Class I and/or MHC Class II binding sites in a wild-type Type II Cas, wherein the engineered Type II Cas has reduced immunogenicity compared to a wild-type Type II Cas.
The engineered Type II Cas of any of the preceding claims, wherein the Type II Cas is a Cas9.
The engineered Type II Cas of any one of the preceding claims, wherein the one or more epitopes corresponding to one or more MHC Class I and/or MHC Class II binding sites are selected from SaCas9 residues 8-16, 926-934, and/or 1034-1042, or residues in another Type II Cas analogous thereto.
The engineered Type II Cas of any one of the preceding claims comprising one or more additional modifications that increase nuclease efficiency, RNA binding efficiency, reduce off-target nuclease activity, or any combination thereof.
The engineered Type II Cas of anyone of the preceding claims, wherein the Cas is a nickase or catalytically inactive (dCas).
The engineered Type II Cas of anyone of the preceding claims, wherein the Cas is further linked to or otherwise capable of associating with a heterologous functional domain.
Dependencies are inferred from the claim text.