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- Title
Trans-splicing Into Highly Abundant Albumin Transcripts for Production of Therapeutic Proteins In Vivo.
- Authors
Wang, Jun; Mansfield, S. Gary; Cote, Colette A.; Ping Du Jiang; Ke Weng; Amar, Marcelo J. A.; Brewer Jr., Bryan H.; Remaley, Alan T.; McGarrity, Gerard J.; Garcia-Blanco, Mariano A.; Puttaraju, M.
- Abstract
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.Molecular Therapy (2009) 17 2, 343–351 doi:10.1038/mt.2008.260
- Subjects
ALBUMINS; PROTEINS; TOXALBUMINS; LACTALBUMIN; NUCLEIC acids; GENETIC transformation; BIOMOLECULES
- Publication
Molecular Therapy, 2009, Vol 17, Issue 2, p343
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.2008.260