Evidence map›Paper›PMID 32313222›Full record

ArticleNature methods2020

Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types.

Sripriya Ravindra Kumar, Timothy F Miles, Xinhong Chen, David Brown, Tatyana Dobreva, Qin Huang, Xiaozhe Ding, Yicheng Luo, Pétur H Einarsson, Alon Greenbaum and 3 more

Abstract read
In one paragraph

Article in Nature methods, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed
–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

122 citing papers in PubMed.

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62 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

13 authors.

Sripriya Ravindra KumarDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-6033-7631
Timothy F Miles *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-6591-3271
Xinhong Chen *Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0003-0408-0813
David BrownDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Tatyana DobrevaDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Qin HuangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Xiaozhe DingDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0002-0267-0791
Yicheng LuoDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0003-3704-2389
Pétur H EinarssonDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Alon GreenbaumDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Min J JangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Benjamin E DevermanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. viviana@caltech.edu.ORCID http://orcid.org/0000-0001-5868-348X

Funding

Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous SystemOT2OD023848 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EFIMOV, IGOR R, FOWLKES, CHARLESS · 2016 to 2021
$21.4M
Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous SystemOT2OD024899 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MULUGETA, MILLION, TACHE, YVETTE FRANCE · 2017 to 2021
$13.1M
Circuit-Specific Delivery of Large Cargo Across the Nervous Systems of Adult Mammals and Embryos via Novel Engineered Systemic VectorsDP1NS111369 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2023
$5.9M
Neuromodulation and Neurodegeneration: the Missing Link and Mechanisms of ActionDP2NS087949 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2013 to 2019
$4.1M
Noninvasive Gene Delivery for Monitoring and Perturbing Cell Types and Circuits in Transgenic and Non-Transgenic AnimalsRF1MH117069 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2018
$2.3M
NIH HHS OT2 OD023848NIH HHS OT2 OD024899NIMH NIH HHS RF1 MH117069NINDS NIH HHS DP1 NS111369NINDS NIH HHS DP2 NS087949
6 · The paper itself

Abstract

Recombinant adeno-associated viruses (rAAVs) are efficient gene delivery vectors via intravenous delivery; however, natural serotypes display a finite set of tropisms. To expand their utility, we evolved AAV capsids to efficiently transduce specific cell types in adult mouse brains. Building upon our Cre-recombination-based AAV targeted evolution (CREATE) platform, we developed Multiplexed-CREATE (M-CREATE) to identify variants of interest in a given selection landscape through multiple positive and negative selection criteria. M-CREATE incorporates next-generation sequencing, synthetic library generation and a dedicated analysis pipeline. We have identified capsid variants that can transduce the central nervous system broadly, exhibit bias toward vascular cells and astrocytes, target neurons with greater specificity or cross the blood-brain barrier across diverse murine strains. Collectively, the M-CREATE methodology accelerates the discovery of capsids for use in neuroscience and gene-therapy applications.

Indexed as

Gene Transfer TechniquesAnimalsBlood-Brain BarrierBrainCapsid ProteinsDependovirusFemaleGenetic EngineeringGenetic TherapyGenetic VectorsIntegrasesMaleMiceMice, Inbred C57BLOrgan SpecificityViral TropismCapsid ProteinsCre recombinaseIntegrases

Identifiers

PMID32313222
PMCPMC7219404

What OpenQuestion holds

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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.