CoChat
Sign Up
Cited by 261Virus-based gene therapy researchRNA Interference and Gene DeliveryNanoparticle-Based Drug Delivery

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 access
Li, Wuping, Asokan, Aravind, Wu, Zhijian, Van Dyke, Terry, DiPrimio, Nina, Johnson, Jarrod S, Govindaswamy, Lakshmanan, Agbandje-McKenna, Mavis, Leichtle, Stefan, Eugene Redmond Jr, D, McCown, Thomas J, Petermann, Kimberly B, Sharpless, Norman E, Samulski, Richard J·2008·Molecular Therapy
DOI 10.1038/mt.2008.100PMC PMC2632803
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Overview

Integrity signals

Registry

Crossref · 10.1038/mt.2008.100

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

Sorted by citations

See all 261

Related

See all

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)
DOI
10.1038/mt.2008.100
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review