An engineered ligand-responsive Csy4 endoribonuclease controls transgene expression from Sendai virus vectors.

ABSTRACT:

Background

Viral vectors are attractive gene delivery vehicles because of their broad tropism, high transduction efficiency, and durable expression. With no risk of integration into the host genome, the vectors developed from RNA viruses such as Sendai virus (SeV) are especially promising. However, RNA-based vectors have limited applicability because they lack a convenient method to control transgene expression by an external inducer.

Results

We engineered a Csy4 switch in Sendai virus-based vectors by combining Csy4 endoribonuclease with mutant FKBP12 (DD: destabilizing domain) that becomes stabilized when a small chemical Shield1 is supplied. In this Shield1-responsive Csy4 (SrC) switch, Shield1 increases Csy4 fused with DD (DD-Csy4), which then cleaves and downregulates t

SUBMITTER: Kishimoto T 

PROVIDER: S-EPMC10790456 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature