The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Engineering and Selection of Shuffled AAV Genomes: A New Strategy for Producing Targeted Biological Nanoparticles
Open accessAbstract
We report a DNA shuffling-based approach for developing cell type-specific vectors through directed evolution. Capsid genomes of adeno-associated virus (AAV) serotypes 1-9 were randomly fragmented and reassembled using PCR to generate a chimeric capsid library. A single infectious clone (chimeric-1829) containing genome fragments from AAV1, 2, 8, and 9 was isolated from an integrin minus hamster melanoma cell line previously shown to have low permissiveness to AAV. Molecular modeling studies suggest that AAV2 contributes to surface loops at the icosahedral threefold axis of symmetry, while AAV1 and 9 contribute to two- and fivefold symmetry interactions, respectively. The C-terminal domain (AAV9) was identified as a critical structural determinant of melanoma tropism through rational mutagenesis. Chimeric-1829 utilizes heparan sulfate as a primary receptor and transduces melanoma cells more efficiently than all serotypes. Further, chimeric-1829 demonstrates altered tropism in rodent skeletal muscle, liver, and brain including nonhuman primates. We determined a unique immunological profile based on neutralizing antibody (NAb) titer and crossreactivity studies strongly supporting isolation of a synthetic laboratory-derived capsid variant. Application of this technology to alternative cell/tissue types using AAV or other viral capsid sequences is likely to yield a new class of biological nanoparticles as vectors for human gene transfer.
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“A novel variant selected from this screen-chimeric-1829-showed higher transduction efficiency and low cross-reactivity with the pre-existing antibodies against other serotypes, indicating that the immune response may not recognize chimeric-1829 [90].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [90]
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Cites
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Schwede, T. F. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg520 · Cited by 5,592
Rapid evolution of a protein in vitro by DNA shuffling
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Self-citationXiao, X., Li, J., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2224-2232.1998 · Cited by 1,381
Self-citationImproved Green Fluorescent Protein by Molecular Evolution Using DNA Shuffling
Crameri, A., Whitehorn, E. A., Tate, E. H., & Stemmer, W. P. C. (1996) · Nature Biotechnology · doi:10.1038/nbt0396-315 · Cited by 1,187
Adeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy
Wu, Z., Asokan, A., & Samulski, R. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.05.009 · Cited by 957
Self-citationDNA shuffling of a family of genes from diverse species accelerates directed evolution
Crameri, A., Raillard, S. A., Bermudez, E., & Stemmer, W. P. C. (1998) · Nature · doi:10.1038/34663 · Cited by 826
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Unraveling hot spots in binding interfaces: progress and challenges
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Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456
Adeno-associated virus as a delivery vector for gene therapy of human diseases
Wang, J.-H., Gessler, D. J., Zhan, W., Gallagher, T. L., & Gao, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01780-w · Cited by 904
Engineering adeno-associated viruses for clinical gene therapy
Kotterman, M. A., & Schaffer, D. V. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3742 · Cited by 761
State-of-the-art gene-based therapies: the road ahead
Kay, M. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2971 · Cited by 698
AAV-Mediated Gene Therapy for Research and Therapeutic Purposes
Samulski, R. J., & Muzyczka, N. (2014) · Annual Review of Virology · doi:10.1146/annurev-virology-031413-085355 · Cited by 609
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Metadata
- Authors
- Li, W., Asokan, A., Wu, Z., Van Dyke, T., DiPrimio, N., Johnson, J. S., Govindaswamy, L., Agbandje-McKenna, M., Leichtle, S., Eugene Redmond Jr, D., McCown, T. J., Petermann, K. B., Sharpless, N. E., & Samulski, R. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Florida (US)
- Yale University (US)
- Corresponding author
- Samulski, Richard J
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 16
- Issue
- 7
- Pages
- 1252-1260
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2632803
- OpenAlex
- W2113082692
- Cited by
- 261
- References
- 49
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 13 · 2023: 6 · 2022: 16 · 2021: 11 · 2020: 10 · 2019: 15 · 2018: 12 · 2017: 14 · 2016: 9 · 2015: 15 · 2014: 16 · 2013: 14 · 2012: 24
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL051818, HL51818)
- National Institute of Allergy and Infectious Diseases (R01AI072176)
- National Institute of Neurological Disorders and Stroke (NS 35633, NS59518, R21NS059518, R01NS035633)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR055712, AR055712)
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- adeno-associated virus, DNA shuffling, directed evolution, heparan sulfate receptor, capsid structure, neutralizing antibodies, gene delivery vectors, biological nanoparticles, AAV serotypes
- MeSH terms
- Dependovirus, Animals, Antibodies, Brain, Capsid, Genetic Vectors, Cricetinae, Humans, Liver, Melanoma, Mice, Inbred BALB C, Primates, Transduction, Genetic, Gene Library, Genome, Viral, Muscle, Skeletal, Directed Molecular Evolution, DNA Shuffling, Mice, Virus Internalization, Nanoparticles
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