Mitochondrial targeted RNA expression system and use thereof

摘要

Described herein is a mitochondrial-targeted RNA expression system (mtTRES) for delivery of RNA molecules to mitochondria. mtTRES vectors generate RNAs in vivo that are un-capped, non-polyadenylated, and actively directed to mitochondria. The disclosed vectors are capable of delivering either non-coding RNA molecules or RNA molecules encoding a protein of interest to the mitochondria. In particular, the disclosed vectors include (1) an RNAPIII initiation (promoter) sequence, (2) a non-coding leader sequence (NCL), (3) a mitochondrial translation initiation sequence and an ORF encoding a protein of interest, or a sequence encoding a non-coding RNA, and (4) an RNAPIII termination sequence.

主权项

1. A vector comprising in the 5′ to 3′ direction:
an RNA polymerase III (RNAPIII) promoter sequence; a non-coding mitochondrial leader sequence; a mitochondrial translation initiation sequence and an open reading frame (ORF) encoding a protein, or a sequence encoding a non-coding RNA molecule capable of inhibiting translation of a mitochondrial mRNA molecule; and an RNAPIII termination sequence, wherein the RNAPIII promoter sequence is a 5S rRNA RNAPIII promoter sequence at least 95% identical to SEQ ID NO: 9.