Evidence map›Paper›PMID 36417917›Full record

ArticleMed (New York, N.Y.)2023

Systemic administration of novel engineered AAV capsids facilitates enhanced transgene expression in the macaque CNS.

Alexandra C Stanton, Kim A Lagerborg, Liana Tellez, Allison Krunnfusz, Emily M King, Simon Ye, Isaac H Solomon, Mohammadsharif Tabebordbar, Pardis C Sabeti

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

Article in Med (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
11.0field-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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  20. Gene Therapy Techniques and Delivery Methods (Review).Sovremennye tekhnologii v meditsine · 2025
    Review
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

9 authors at 2 institutions in 1 country.

Alexandra C StantonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Program in Virology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: acstanton@g.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.
Liana TellezBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Allison KrunnfuszBroad Institute of MIT and Harvard, Cambridge, MA 02142, 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 02142, USA.
Isaac H SolomonHarvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Mohammadsharif TabebordbarBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
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. Electronic address: pardis@broadinstitute.org.
Broad Institute · USBrigham and Women's Hospital · US

Funding

Developing a robust platform to identify unexpected and novel viruses in human brain tissueR21NS119660 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI PIANTADOSI, ANNE L, SOLOMON, ISAAC H. · 2020 to 2020
$480k
Howard Hughes Medical InstituteNINDS NIH HHS R21 NS119660
6 · The paper itself

Abstract

backgroundAdeno-associated virus (AAV) vectors are a promising vehicle for noninvasive gene delivery to the central nervous system via intravenous infusion. However, naturally occurring serotypes have a limited ability to transduce the brain, and translating engineered capsids from mice to nonhuman primates has proved challenging.

methodsIn this study, we use an mRNA-based directed-evolution strategy in multiple strains of mice as well as a de novo selection in cynomolgus macaques to identify families of engineered vectors with increased potency in the brain and decreased tropism for the liver.

findingsWe compare the transgene expression capabilities of several engineered vectors and show that while some of our novel macaque-derived variants significantly outperform AAV9 in transducing the macaque brain following systemic administration, mouse-derived variants-both those identified in this study and those reported by other groups-universally do not.

conclusionsTogether, the results of this work introduce a class of primate-derived engineered AAV capsids with increased therapeutic potential and highlight the critical need for using appropriate animal models to both identify and evaluate novel AAVs intended for delivery to the human central nervous system.

fundingThis work was funded primarily through an anonymous philanthropic gift to the P.C.S. lab at the Broad Institute of MIT and Harvard and by a grant from the Howard Hughes Medical Institute to P.C.S.

Indexed as

CapsidMacacaAnimalsCentral Nervous SystemDependovirusGenetic VectorsHumansMicePrimatesTransgenesAAVbraincapsidcapsid engineeringcentral nervous systemCNSgene therapymacaqueNHPPre-clinical researchsystemic administration

Identifiers

PMID36417917
PMCPMC9840684
OpenAlexW4309593290

What OpenQuestion holds

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LicenceCC BY
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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.