The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index.
Efficient mouse airway transduction following recombination between AAV vectors carrying parts of a larger gene
Abstract
The small packaging capacity of adeno-associated virus (AAV) vectors limits the utility of this promising vector system for transfer of large genes. We explored the possibility that larger genes could be reconstituted following homologous recombination between AAV vectors carrying overlapping gene fragments. An alkaline phosphatase (AP) gene was split between two such AAV vectors (rec vectors) and packaged using AAV2 or AAV6 capsid proteins. Rec vectors having either capsid protein recombined to express AP in cultured cells at about 1-2% of the rate observed for an intact vector. Surprisingly, the AAV6 rec vectors transduced lung cells in mice almost as efficiently as did an intact vector, with 10% of airway epithelial cells, the target for treatment of cystic fibrosis (CF), being positive. Thus AAV rec vectors may be useful for diseases such as CF that require transfer of large genes.
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In the citing paper
“simultaneous infection of cells with two vectors containing an overlapping fragment of 440 or 1000 bases of the AP gene could successfully transduce HT-1080 cells, although only at 1-2% efficiency of a vector that expressed AP from a single vector genome. 43”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [43]
In the citing paper
“In vivo , the best overlapping vector pair yielded almost identical transduction of the airway epithelium when compared with the single-genome virus.”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [43]
In the citing paper
“they could detect transduction only with vector pairs that shared either 440or 1000-base regions of homology but not with vector pairs without homology. 43”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [43]
In the citing paper
“Intracellular vector recombination of AAV vectors has been previously described.7”
From Effect of genome size on AAV vector packaging (2010) · cites this paper as [7]
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Metadata
- Authors
- Halbert, C. L., Allen, J. M., & Miller, A. D.
- Affiliations
- Fred Hutch Cancer Center (US)
- Corresponding author
- Miller, A. Dusty
- Venue
- Nature Biotechnology
- Published
- 2002-07
- Volume
- 20
- Issue
- 7
- Pages
- 697-701
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2042805311
- Cited by
- 121
- References
- 25
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 9 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Earth Sciences
- Ministry of Education, India
- National Institutes of Health
- National Heart, Lung, and Blood Institute (U01HL066947, HL-66947)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-47754, P30DK047754)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- adeno-associated virus vectors, homologous recombination, alkaline phosphatase reporter, airway epithelial cells, cystic fibrosis gene therapy
- MeSH terms
- Dependovirus, Animals, Gene Expression Regulation, Genetic Vectors, Humans, Lung, Mice, Inbred C57BL, Recombination, Genetic, Transduction, Genetic, Respiratory Mucosa, Capsid Proteins, Mice
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