Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo.
Enviado por Mariano Garcia-Blanco el
Título | Trans-splicing into highly abundant albumin transcripts for production of therapeutic proteins in vivo. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Autores | Wang, J, Mansfield, GS, Cote, CA, Jiang, PD, Weng, K, Amar, MJA, Brewer, BH, Remaley, AT, McGarrity, GJ, García-Blanco, MA, Puttaraju, M |
Journal | Mol Ther |
Volume | 17 |
Issue | 2 |
Pagination | 343-51 |
Date Published | 2009 Feb |
ISSN | 1525-0024 |
Palabras clave | Albumins, Animals, Apolipoprotein A-I, Exons, Female, Gene Therapy, Genetic Vectors, Humans, Mice, Mice, Inbred C57BL, Reverse Transcriptase Polymerase Chain Reaction, RNA Precursors, RNA Splicing, Spliceosomes, Trans-Splicing |
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. |
DOI | 10.1038/mt.2008.260 |
Alternate Journal | Mol. Ther. |
PubMed ID | 19066600 |