Ku inhibitors and their use
AssigneeIndiana University Research and Technology Corporation
InventorsJohn J Turchi, Navnath Gavande, Pamela S. Vandervere-Carozza
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Abstract
The present disclosure relates to certain compounds having binding affinity for Ku, and uses thereof. Specifically, the present disclosure relates to the use of Ku inhibitors as described herein in site-specific genome engineering technologies, including but not limited to CRISPR/Cas9, Zinc finger nuclease (ZFN), Transcription activator-like effector nuclease (TALEN), and meganuclease. The present disclosure also relates to kits useful for site-specific genome engineering that include at least one compound as described herein.
Claims20
A method of gene editing comprising
- a. contacting a compound with at least one cell comprising at least one programmable nuclease,
- wherein the at least one programmable nuclease comprises a Cas9 endonuclease;
- and
- wherein the compound is of formula I
- wherein
- X is absent
- Z is O or S;
- R1 is H, —CO2R6, or —S(O)2NR6R7;
- R2 is H, —CO2R6, —CN, or tetrazolyl;
- R3 is C1-C6 alkyl;
- R4 is selected from the group consisting of
- R5 is H;
- R6 and R7 are each independently H, or C1-C6 alkyl;
- R10 is halogen;
- “*” represents the point of attachment as indicated in Formula I;
- and
- is either a single bond or a pi-bond;
- and
- b. contacting the at least one cell with a plasmid encoding a guide RNA (gRNA) comprising a Clustered Regularly Interspaced Short Palindromic repeat RNA (crRNA) and a trans-activating RNA (tracrRNA).
A method of gene editing comprising
- a. contacting a compound with at least one cell comprising at least one programmable nuclease,
- wherein the at least one programmable nuclease comprises a Cas9 endonuclease;
- and
- wherein the compound is of formula I
- wherein
- X is absent,
- Z is O or S;
- R1 is H, —CO2H, —S(O)2NH2, or —CO2Et;
- R2 is H, —CO2H, —CO2Et, —CN, or tetrazolyl;
- R3 is methyl;
- R4 is selected from the group consisting of
- “*” represents the point of attachment as indicated in Formula I;
- and
- is either a single bond or a pi-bond;
- and
- b. contacting the at least one cell with a plasmid encoding a guide RNA (gRNA) comprising a Clustered Regularly Interspaced Short Palindromic repeat RNA (crRNA) and a trans-activating RNA (tracrRNA).
Dependencies are inferred from the claim text.