The present disclosure relates to engineered polypeptides comprising degradation domains, compounds, compositions, and methods for their preparation and use as for degrading engineered proteins in cells.

1. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63/230,225, filed Aug. 6, 2021, which is incorporated by reference here in its entirety for any purpose.

2. FIELD

[0002] The present disclosure relates to engineered polypeptides comprising degradation domains, compounds, compositions, and methods for their preparation and use as for degrading engineered proteins in cells.

3. BACKGROUND

[0003] Engineered cells comprising an engineered, heterologous polypeptide, such as chimeric antigen receptor T (CAR-T) cells, have been developed for therapeutic use. Modulation of the expression levels of such engineered, heterologous polypeptides may improve the therapeutic benefit of the engineered cells by, for example, decreasing side effects and/or increasing efficacy of the engineered cells.

[0004] Accordingly, in one aspect, provided herein are engineered polypeptides and degradation agents, wherein the engineered polypeptides comprise a degradation domain that mediates ubiquitination in cell when the degradation domain binds to a degradation agent.

4. SUMMARY

[0005] Described herein, in certain embodiments, are compounds and compositions thereof for modulating levels of a heterologous polypeptide in a cell. In various embodiments, the compounds and compositions thereof may be used to decrease the level of the heterologous polypeptide in the cell.

[0006] The present embodiments can be understood more fully by reference to the detailed description and examples, which are intended to exemplify non-limiting embodiments.