Zinc Finger Degradation Domains

Synthetic zinc finger degrons, and their use with non-naturally occurring or engineered programmable nucleases are provided, allowing specific targeting of the engineered programmable nucleases for control of gene editing outcomes when provided with small molecules such as immunomodulatory inducing drugs (IMiDs) that can control or modulate Cas variant proteins that comprise one or more hybrid zinc fingers, as detailed in Jan et al., Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide. Sci Transl Med. 2021 Jan 6;13(575):eabb6295. doi: 10.1126/scitranslmed.abb6295. .