Evidence map›Paper›PMID 26235624›Full record

ArticleCell reports2015

In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector.

Eric Zinn, Simon Pacouret, Vadim Khaychuk, Heikki T Turunen, Livia S Carvalho, Eva Andres-Mateos, Samiksha Shah, Rajani Shelke, Anna C Maurer, Eva Plovie and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

192 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Identification of CD164 as an essential entry receptor for divergent adeno-associated viruses.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. The rise of cochlear gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  15. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  16. Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  17. Article
  18. Review
  19. Review
  20. Review

132 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Eric ZinnGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Simon PacouretGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Vadim KhaychukGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Heikki T TurunenGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Livia S CarvalhoGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Eva Andres-MateosGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Samiksha ShahGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Rajani ShelkeGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Anna C MaurerGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Eva PlovieGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Ru XiaoGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA.
Luk H VandenbergheGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: luk_vandenberghe@meei.harvard.edu.

Funding

Broad Spectrum Molecular Therapy for Blinding Retina DisordersDP1EY023177 · NEI · UNIVERSITY OF PENNSYLVANIA · PI BENNETT, JEAN · 2012 to 2015
$3.2M
Broad Spectrum Molecular Therapy for Blinding Retina DisordersDP1OD008267 · OD · UNIVERSITY OF PENNSYLVANIA · PI BENNETT, JEAN · 2011 to 2011
$800k
NCCDPHP CDC HHS 5DP1EY023177-03NEI NIH HHS DP1 EY023177NIH HHS DP1 OD008267
6 · The paper itself

Abstract

Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina.

Indexed as

Gene Transfer TechniquesDependovirusGenetic TherapyGenetic VectorsMolecular Sequence Data

Identifiers

PMID26235624
PMCPMC4536165

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.