StaPLs: versatile genetically encoded modules for engineering drug-inducible proteins

Conor L Jacobs; Ryan K Badiee; Michael Z Lin

doi:10.1038/s41592-018-0041-z

StaPLs: versatile genetically encoded modules for engineering drug-inducible proteins

Nat Methods. 2018 Jul;15(7):523-526. doi: 10.1038/s41592-018-0041-z. Epub 2018 Jul 2.

Authors

Conor L Jacobs^{1

2

3}, Ryan K Badiee^{2

3

4

5}, Michael Z Lin^{6

7

8}

Affiliations

¹ Graduate Program in Biological Sciences, Stanford University, Stanford, CA, USA.
² Department of Neurobiology, Stanford University, Stanford, CA, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁴ Department of Biology, Stanford University, Stanford, CA, USA.
⁵ MD Program, University of California San Francisco School of Medicine, San Francisco, CA, USA.
⁶ Department of Neurobiology, Stanford University, Stanford, CA, USA. mzlin@stanford.edu.
⁷ Department of Bioengineering, Stanford University, Stanford, CA, USA. mzlin@stanford.edu.
⁸ Department of Pediatrics, Stanford University, Stanford, CA, USA. mzlin@stanford.edu.

Abstract

Robust approaches for chemogenetic control of protein function would have many biological applications. We developed stabilizable polypeptide linkages (StaPLs) based on hepatitis C virus protease. StaPLs undergo autoproteolysis to cleave proteins by default, whereas protease inhibitors prevent cleavage and preserve protein function. We created StaPLs responsive to different clinically approved drugs to bidirectionally control transcription with zinc-finger-based effectors, and used StaPLs to create single-chain, drug-stabilizable variants of CRISPR-Cas9 and caspase-9.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

CRISPR-Cas Systems
Dimerization
Gene Expression Regulation / drug effects*
Gene Targeting
HEK293 Cells
HeLa Cells
Humans
Plasmids
Protein Engineering*
Protein Folding
Viral Nonstructural Proteins / metabolism
Zinc Fingers

Substances

NS3 protein, hepatitis C virus
Viral Nonstructural Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding