Cited by 356Virus-based gene therapy researchRNA Interference and Gene DeliveryCRISPR and Genetic Engineering

Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design

Open access
Ogden, Pierce J., Kelsic, Eric D., Sinai, Sam, Church, George M.·2019·Science

Abstract

The fitness landscape of AAV: Adeno-associated virus (AAV) is an important gene therapy vector. Using tools from synthetic biology, Ogden et al. provide a comprehensive view of how sequence changes in capsid proteins affect AAV properties. After saturation mutagenesis of the AAV2 capsid gene, the resulting library was subjected to multiplexed phenotypic analyses, including virus production, immunity, thermostability, and biodistribution. The mutant distribution to major organs in mice revealed dominant trends affecting in vivo delivery. Moreover, the findings uncovered a viral accessory protein with a role in viral production. Finally, a model built from the capsid fitness landscape enabled machine-guided design of useful variants with much higher efficiency than random mutagenesis. Science , this issue p. 1139

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1126/science.aaw2900

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Ogden, P. J., Kelsic, E. D., Sinai, S., & Church, G. M.
Affiliations
Harvard University (US)
Corresponding author
  • Ogden, Pierce J.
  • Kelsic, Eric D.
  • Church, George M.
Venue
Science
Published
2019-11-29
Volume
366
Issue
6469
Pages
1139-1143
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2991022372
Cited by
356
References
21
Citations by year
2026: 41 · 2025: 50 · 2024: 72 · 2023: 52 · 2022: 46 · 2021: 66 · 2020: 28
FWCI
21.08
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH Office of the Director (HG005550, HG008525)
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 › CRISPR and Genetic Engineering
Keywords
adeno-associated virus, accessory proteins, competitive exclusion, viral gene expression, tissue distribution, gene therapy vectors
MeSH terms
Dependovirus, Capsid, Genes, Viral, Humans, Transfection, Protein Engineering, Genetic Therapy, Mutagenesis, Insertional, Sequence Deletion, Capsid Proteins, HEK293 Cells

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