Evidence map›Paper›PMID 34506722›Full record

ArticleCell2021

Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species.

Mohammadsharif Tabebordbar, Kim A Lagerborg, Alexandra Stanton, Emily M King, Simon Ye, Liana Tellez, Allison Krunnfusz, Sahar Tavakoli, Jeffrey J Widrick, Kathleen A Messemer and 8 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 343 papers.

0numbers the graph read from it
0cells of the map it votes in
343citing papers in PubMed
52.6field-weighted citation impact, top 1% of its field
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

343 citing papers in PubMed, 479 citations in OpenAlex.

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  16. Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026
    Review
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  18. Review
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283 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Mohammadsharif TabebordbarBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: tabebord@fas.harvard.edu.
Kim A LagerborgBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Alexandra StantonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
Emily M KingBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Simon YeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Liana TellezBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Allison KrunnfuszBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sahar TavakoliDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Jeffrey J WidrickDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kathleen A MessemerDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
Emily C TroianoDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Behzad MoghadaszadehDivision of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Bryan L PeackerDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
Krystynne A LeacockDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
Naftali HorwitzDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
Alan H BeggsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Amy J WagersDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA 02215, USA. Electronic address: amy_wagers@harvard.edu.
Pardis C SabetiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: pardis@broadinstitute.org.
Broad Institute · USHarvard Stem Cell Institute · USBoston Children's Hospital · US

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Uncovering molecular effectors of mammalian agingDP1AG063419 · NIA · HARVARD UNIVERSITY · PI WAGERS, AMY JO · 2018 to 2022
$5.9M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2M
Howard Hughes Medical InstituteNIA NIH HHS DP1 AG063419NICHD NIH HHS P50 HD105351NICHD NIH HHS U54 HD090255
6 · The paper itself

Abstract

Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly in large, anatomically distributed tissues such as skeletal muscle. Here, we establish an in vivo strategy to evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery to desired tissues. Using this method, we identify a class of RGD motif-containing capsids that transduces muscle with superior efficiency and selectivity after intravenous injection in mice and non-human primates. We demonstrate substantially enhanced potency and therapeutic efficacy of these engineered vectors compared to naturally occurring AAV capsids in two mouse models of genetic muscle disease. The top capsid variants from our selection approach show conserved potency for delivery across a variety of inbred mouse strains, and in cynomolgus macaques and human primary myotubes, with transduction dependent on target cell expressed integrin heterodimers.

Indexed as

Directed Molecular EvolutionGene Transfer TechniquesAmino Acid SequenceAnimalsCapsidCells, CulturedDependovirusDisease Models, AnimalHEK293 CellsHumansIntegrinsMacaca fascicularisMiceMice, Inbred BALB CMice, Inbred C57BLMuscle Fibers, SkeletalIntegrinsmyotubularinProtein Tyrosine Phosphatases, Non-ReceptorAAV capsid engineeringdirected evolutionDuchenne muscular dystrophyintegrin heterodimersmuscle gene therapyMyoAAVnon-human primatesX-linked myotubular myopathy

Identifiers

PMID34506722
PMCPMC9344975
OpenAlexW3198514921

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.