Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy

Ziying Yan; Yulong Zhang; Dongsheng Duan; John F Engelhardt

doi:10.1073/pnas.97.12.6716

Back

Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy

Journal article

Open access

Peer reviewed

Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy

Ziying Yan, Yulong Zhang, Dongsheng Duan and John F Engelhardt

Proceedings of the National Academy of Sciences - PNAS, Vol.97(12), pp.6716-6721

From the Cover

06/06/2000

DOI: 10.1073/pnas.97.12.6716

PMCID: PMC18714

PMID: 10841568

Files and links (1)

url

https://doi.org/10.1073/pnas.97.12.6716View

Published (Version of record) Open Access

Abstract

Adeno-associated viral (AAV) vectors have demonstrated considerable promise for gene therapy of inherited diseases. However, with a packaging size of <5 kb, applications have been limited to relatively small disease genes. Based on the finding that AAV genomes undergo intermolecular circular concatamerization after transduction in muscle, we have developed a paradigm to increase the size of delivered transgenes with this vector through trans-splicing between two independent vectors coadministered to the same tissue. When two vectors encoding either the 5′ or 3′ portions of the erythropoietin genomic locus were used, functional erythropoietin protein was expressed in muscle subsequent to the formation of intermolecular circular concatamers in a head-to-tail orientation through trans-splicing between these two independent vector genomes. These findings will allow for the application of AAV technologies to a wider variety of diseases for which therapeutic transgenes exceed the packaging limitation of present AAV vectors.

Biological Sciences

Details

Title: Subtitle: Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy
Creators: Ziying Yan - Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, and Departments of
Yulong Zhang - Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, and Departments of
Dongsheng Duan - Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, and Departments of
John F Engelhardt - Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, and Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.97(12), pp.6716-6721
Series: From the Cover
DOI: 10.1073/pnas.97.12.6716
PMID: 10841568
PMCID: PMC18714
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 06/06/2000
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984025301102771

Metrics

23 Record Views

223 Times Cited - Web of Science