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Record W2140320479 · doi:10.15252/emmm.201404077

Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno‐associated virus capsid and promoter

2014· article· en· W2140320479 on OpenAlexaff
Thérèse Cronin, Luk H. Vandenberghe, Péter Hantz, Josephine Jüttner, Andreas Reimann, Ágota–Enikő Kacsó, Rachel M. Huckfeldt, Volker Busskamp, Hubertus Kohler, Pamela S. Lagali, Botond Roska, Jean Bennett

Bibliographic record

VenueEMBO Molecular Medicine · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRetinal Development and Disorders
Canadian institutionsOttawa Hospital
FundersPerelman School of Medicine, University of PennsylvaniaNational Eye InstituteJames N. Kirby FoundationHope For VisionUniversity of PennsylvaniaResearch to Prevent BlindnessNational Center for Chronic Disease Prevention and Health PromotionSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungF. M. Kirby FoundationNational Institutes of HealthNational Science Foundation
KeywordsOptogeneticsTransduction (biophysics)Adeno-associated virusCapsidRetinalBiologyTransgeneCell biologyNeuroscienceVirusVector (molecular biology)VirologyGeneGeneticsRecombinant DNABiophysics

Abstract

fetched live from OpenAlex

In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (~100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.000
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.213
Teacher spread0.209 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations184
Published2014
Admission routes1
Has abstractyes

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Same venueEMBO Molecular MedicineSame topicRetinal Development and DisordersFrench-language works237,207