Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo

Jun Wang, Gary S. Mansfield, Colette A. Cote, Ping Du Jiang, Ke Weng, Marcelo J.A. Amar, Bryan H. Brewer, Alan T. Remaley, Gerard J. McGarrity, Mariano A. Garcia-Blanco, M. Puttaraju

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)343-351
Number of pages9
JournalMolecular Therapy
Volume17
Issue number2
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo'. Together they form a unique fingerprint.

  • Cite this

    Wang, J., Mansfield, G. S., Cote, C. A., Jiang, P. D., Weng, K., Amar, M. J. A., Brewer, B. H., Remaley, A. T., McGarrity, G. J., Garcia-Blanco, M. A., & Puttaraju, M. (2009). Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo. Molecular Therapy, 17(2), 343-351. https://doi.org/10.1038/mt.2008.260