TY - JOUR
T1 - Alternative splicing in disease and therapy
AU - Garcia-Blanco, Mariano A.
AU - Baraniak, Andrew P.
AU - Lasda, Erika L.
N1 - Funding Information:
The authors thank Ed Otto and Jean-Marc Gallo for critically reading the manuscript, and members of the Garcia-Blanco laboratory for helpful suggestions. The authors also thank Annette Kennett for help in preparing the manuscript and Candy Webster for expert work on the figures. M.A.G.-B. acknowledges support from National Institutes of Health grants RO1 GM63090 and R33 CA97502.
PY - 2004/5
Y1 - 2004/5
N2 - Alternative splicing is the major source of proteome diversity in humans and thus is highly relevant to disease and therapy. For example, recent work suggests that the long-sought-after target of the analgesic acetaminophen is a neural-specific, alternatively spliced isoform of cyclooxygenase 1 (COX-1). Several important diseases, such as cystic fibrosis, have been linked with mutations or variations in either cis-acting elements or trans-acting factors that lead to aberrant splicing and abnormal protein production. Correction of erroneous splicing is thus an important goal of molecular therapies. Recent experiments have used modified oligonucleotides to inhibit cryptic exons or to activate exons weakened by mutations, suggesting that these reagents could eventually lead to effective therapies.
AB - Alternative splicing is the major source of proteome diversity in humans and thus is highly relevant to disease and therapy. For example, recent work suggests that the long-sought-after target of the analgesic acetaminophen is a neural-specific, alternatively spliced isoform of cyclooxygenase 1 (COX-1). Several important diseases, such as cystic fibrosis, have been linked with mutations or variations in either cis-acting elements or trans-acting factors that lead to aberrant splicing and abnormal protein production. Correction of erroneous splicing is thus an important goal of molecular therapies. Recent experiments have used modified oligonucleotides to inhibit cryptic exons or to activate exons weakened by mutations, suggesting that these reagents could eventually lead to effective therapies.
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U2 - 10.1038/nbt964
DO - 10.1038/nbt964
M3 - Review article
C2 - 15122293
AN - SCOPUS:2342450548
SN - 1087-0156
VL - 22
SP - 535
EP - 546
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 5
ER -