Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo.
Journal Article (Journal Article)
Spliceosome-mediated RNA trans-splicing has emerged as an exciting mode of RNA therapy. Here we describe a novel trans-splicing strategy, which targets highly abundant pre-mRNAs, to produce therapeutic proteins in vivo. First, we used a pre-trans-splicing molecule (PTM) that mediated trans-splicing of human apolipoprotein A-I (hapoA-I) into the highly abundant mouse albumin exon 1. Hydrodynamic tail vein injection of the hapoA-I PTM plasmid in mice followed by analysis of the chimeric transcripts and protein, confirmed accurate and efficient trans-splicing into albumin pre-mRNA and production of hapoA-I protein. The versatility of this approach was demonstrated by producing functional human papillomavirus type-16 E7 (HPV16-E7) single-chain antibody in C57BL/6 mice and functional factor VIII (FVIII) and phenotypic correction in hemophilia A mice. Altogether, these studies demonstrate that trans-splicing to highly abundant albumin transcripts can be used as a general platform to produce therapeutic proteins in vivo.
Full Text
Duke Authors
Cited Authors
- Wang, J; Mansfield, SG; Cote, CA; Jiang, PD; Weng, K; Amar, MJA; Brewer, BH; Remaley, AT; McGarrity, GJ; Garcia-Blanco, MA; Puttaraju, M
Published Date
- February 2009
Published In
Volume / Issue
- 17 / 2
Start / End Page
- 343 - 351
PubMed ID
- 19066600
Pubmed Central ID
- PMC2835072
Electronic International Standard Serial Number (EISSN)
- 1525-0024
Digital Object Identifier (DOI)
- 10.1038/mt.2008.260
Language
- eng
Conference Location
- United States