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


  • eng

Conference Location

  • United States