Targeted disruption of the mhc cell receptor
AssigneeSangamo Therapeutics, Inc.
InventorsGary K. Lee, David Paschon, Lei Zhang
Life of this patent
Estimating the term…
Abstract
Disclosed herein are methods and compositions for inactivating MHC genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.
Claims20
An isolated lymphoid cell, induced pluripotent stem cell (iPSC), mesenchymal stem cell (MSC), hematopoietic stem cell (HSC) or progenitor cell in which expression of a beta 2 microglobulin (B2M) gene is partially or completely inactivated by an insertion and/or a deletion within TCAAAT (designated as site D in FIG. 1B) or TCAAATT (designated as cite C in FIG. 1B), of exon 2 of the B2M gene, wherein the insertion and/or deletion is made by an exogenous fusion molecule comprising a zinc finger protein (ZFP) or transcription activator-like effector (TALE) DNA-binding domain that binds to a target site as shown in SEQ ID NO:
- 8, 9, 10 or 11 and a cleavage domain or a cleavage half-domain;
- wherein when the cleavage site is TCAAAT, the target site is SEQ ID NO:
- 8 or SEQ ID NO:
- 9;
- and
- wherein when the cleavage site is TCAAATT, the target site is SEQ ID NO:
- 9 or SEQ ID NO:10.
A fusion molecule comprising a DNA-binding domain that binds to exon 2 of a B2M gene and a cleavage domain or cleavage half-domain, wherein the DNA-binding domain comprises a ZFP with six zinc fingers designated F1-F6 in the order F1-F6 for the ZFP designated as SBS57017, SBS57332, SBS57469 or SBS57331 in a single row of Table 1;
- or a TALE protein with the repeat variable diresidues for the TALE designated as 103076, 103077, 103079, 103081, 103083, 103085, or 103087 s shown in a single row of Table 2B.
Dependencies are inferred from the claim text.