Evidence map›Paper›PMID 36702899›Full record

ArticleNature biotechnology2023

Spatial transcriptomics for profiling the tropism of viral vectors in tissues.

Min J Jang, Gerard M Coughlin, Cameron R Jackson, Xinhong Chen, Miguel R Chuapoco, Julia L Vendemiatti, Alexander Z Wang, Viviana Gradinaru

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
15.7field-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

43 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  7. Defining a Midgestational Window forbioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Min J JangDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Gerard M CoughlinDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Cameron R JacksonDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Xinhong ChenDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0003-0408-0813
Miguel R ChuapocoDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Julia L VendemiattiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Alexander Z WangDivision of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.ORCID http://orcid.org/0000-0001-7375-5445
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
California Institute of Technology · US

Funding

Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across SpeciesUF1MH128336 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI FOX, ANDREW S, GRADINARU, VIVIANA · 2021 to 2021
$6.1M
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
Multiplex interrogation of neuromodulatory signaling in behaving animals with enhanced depth and resolutionU01NS120820 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TIAN, LIN, VONZASTROW, MARK E · 2021 to 2024
$3.5M
NIMH NIH HHS UF1 MH128336NINDS NIH HHS DP1 NS111369NINDS NIH HHS U01 NS120820
6 · The paper itself

Abstract

A barrier to advancing engineered adeno-associated viral vectors (AAVs) for precision access to cell subtypes is a lack of high-throughput, high-resolution assays to characterize in vivo transduction profiles. In this study, we developed an ultrasensitive, sequential fluorescence in situ hybridization (USeqFISH) method for spatial transcriptomic profiling of endogenous and viral RNA with a short barcode in intact tissue volumes by integrating hydrogel-based tissue clearing, enhanced signal amplification and multiplexing using sequential labeling. Using USeqFISH, we investigated the transduction and cell subtype tropisms across mouse brain regions of six systemic AAVs, including AAV-PHP.AX, a new variant that transduces robustly and efficiently across neurons and astrocytes. Here we reveal distinct cell subtype biases of each AAV variant, including a bias of AAV-PHP.N toward excitatory neurons. USeqFISH also enables profiling of pooled regulatory cargos, as we show for a 13-variant pool of microRNA target sites in AAV genomes. Lastly, we demonstrate potential applications of USeqFISH for in situ AAV profiling and multimodal single-cell analysis in non-human primates.

Indexed as

Gene Transfer TechniquesTranscriptomeAnimalsDependovirusGenetic VectorsIn Situ Hybridization, FluorescenceMiceTransduction, GeneticTropismViral Tropism

Identifiers

PMID36702899
PMCPMC10443732
OpenAlexW4318071669

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.