Antisense derivatives of U7 and other small nuclear RNAs as tools to modify pre-mRNA splicing patterns

Asparuhova, Maria B.; Kole, Ryszard; Schümperli, Daniel (2004). Antisense derivatives of U7 and other small nuclear RNAs as tools to modify pre-mRNA splicing patterns. Gene Therapy and Regulation, 2(4), pp. 321-349. VSP International Science Publishers 10.1163/1568558043967472

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The importance of alternative splicing for the diversity of the proteome and the large number of genetic diseases that are due to splicing defects call for methods to modulate alternative splicing decisions. Although splicing can be modulated by antisense oligonucleotides, this approach is confronted with problems of efficient delivery and the need for repeated administrations of large amounts of the oligonucleotides. Therefore we have developed methods allowing us to modulate splicing with the help of modified derivatives of the U7 small nuclear RNA involved in histone RNA 3' end processing. Its nuclear accumulation as a stable ribonucleoprotein particle makes U7 snRNA especially useful for this purpose. In particular, U7 derivatives containing two tandem antisense sequences directed against targets upstream and downstream of an exon can induce the efficient and specific skipping of that exon. U7 expression cassettes have been successfully introduced into a great number of cell lines, primary cells or tissues with the help of lentiviral and adeno-associated viral vectors. Examples of these therapeutic strategies in the fields of β-thalassemia, Duchenne muscular dytrophy and HIV/AIDS are discussed.

Item Type:

Journal Article (Review Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Schümperli, Daniel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1388-9532

Publisher:

VSP International Science Publishers

Language:

English

Submitter:

Daniel Schümperli

Date Deposited:

12 May 2015 08:02

Last Modified:

20 Nov 2017 08:25

Publisher DOI:

10.1163/1568558043967472

BORIS DOI:

10.7892/boris.68857

URI:

https://boris.unibe.ch/id/eprint/68857

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