Doxycycline-controlled splicing modulation by regulated antisense U7 snRNA expression cassettes
نویسندگان
چکیده
منابع مشابه
Rescue of a severe mouse model for spinal muscular atrophy by U7 snRNA-mediated splicing modulation.
In spinal muscular atrophy (SMA), the leading genetic cause of early childhood death, the survival motor neuron 1 gene (SMN1) is deleted or inactivated. The nearly identical SMN2 gene has a silent mutation that impairs the utilization of exon 7 and the production of functional protein. It has been hypothesized that therapies boosting SMN2 exon 7 inclusion might prevent or cure SMA. Exon 7 inclu...
متن کاملCorrection of SMN2 Pre-mRNA splicing by antisense U7 small nuclear RNAs.
Mutations in one of the duplicated survival of motor neuron (SMN) genes lead to the progressive loss of motor neurons and subsequent development of spinal muscular atrophy (SMA), a common, and usually fatal, hereditary disease. Homozygous absence of the telomeric copy (SMN1) correlates with development of SMA because differential splicing of the centromeric copy (SMN2) leads to exon 7 skipping ...
متن کاملThe Cellular Processing Capacity Limits the Amounts of Chimeric U7 snRNA Available for Antisense Delivery
Many genetic diseases are induced by mutations disturbing the maturation of pre-mRNAs, often affecting splicing. Antisense oligoribonucleotides (AONs) have been used to modulate splicing thereby circumventing the deleterious effects of mutations. Stable delivery of antisense sequences is achieved by linking them to small nuclear RNA (snRNAs) delivered by viral vectors, as illustrated by studies...
متن کاملSomatic Therapy of a Mouse SMA Model with a U7 snRNA Gene Correcting SMN2 Splicing
Spinal Muscular Atrophy is due to the loss of SMN1 gene function. The duplicate gene SMN2 produces some, but not enough, SMN protein because most transcripts lack exon 7. Thus, promoting the inclusion of this exon is a therapeutic option. We show that a somatic gene therapy using the gene for a modified U7 RNA which stimulates this splicing has a profound and persistent therapeutic effect on th...
متن کاملRescue of dystrophic muscle through U7 snRNA-mediated exon skipping.
Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mous...
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ژورنال
عنوان ژورنال: Gene Therapy
سال: 2008
ISSN: 0969-7128,1476-5462
DOI: 10.1038/gt.2008.138