Evidence map›Paper›PMID 36947856›Full record

ArticleChembiochem : a European journal of chemical biology2023

The Wild-Type tRNA Adenosine Deaminase Enzyme TadA Is Capable of Sequence-Specific DNA Base Editing.

Brodie L Ranzau, Kartik L Rallapalli, Mallory Evanoff, Francesco Paesani, Alexis C Komor

Open access · bronzeAbstract read
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 10 citations in OpenAlex.

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  10. MutaT7ACS synthetic biology · 2024
    Article
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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

5 authors at 2 institutions in 1 country.

Brodie L RanzauDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-6170-7187
Kartik L RallapalliDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-7402-1187
Mallory EvanoffDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-6399-7731
Francesco PaesaniDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-4451-1203
Alexis C KomorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-5043-0998
University of California San Diego · USSan Diego Supercomputer Center · US

Funding

GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
Supplement to R35 "Development and Application of New Genome Editing Tools for the Functional Investigation of Genetic Variants of Uncertain Significance"R35GM138317 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Alexis C. Komor · 2020 to 2026
$2.8M
Chemistry-Biology Interfaces at UCSDT32GM146648 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael D. Burkart, Alexis C. Komor · 2022 to 2026
$876k
Chemical Biology Interfaces at UC San DiegoT32GM112584 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BURKART, MICHAEL D. · 2015 to 2019
$729k
NIGMS NIH HHS R35 GM138317NIGMS NIH HHS T32 GM007240NIGMS NIH HHS T32 GM112584NIGMS NIH HHS T32 GM146648
6 · The paper itself

Abstract

Base editors are genome editing tools that enable site-specific base conversions through the chemical modification of nucleobases in DNA. Adenine base editors (ABEs) convert A ⋅ T to G ⋅ C base pairs in DNA by using an adenosine deaminase enzyme to modify target adenosines to inosine intermediates. Due to the lack of a naturally occurring adenosine deaminase that can modify DNA, ABEs were evolved from a tRNA-deaminating enzyme, TadA. Previous experiments with an ABE comprising a wild-type (wt) TadA showed no detectable activity on DNA, and directed evolution was therefore required to enable this enzyme to accept DNA as a substrate. Here we show that wtTadA can perform base editing in DNA in both bacterial and mammalian cells, with a strict sequence motif requirement of TAC. We leveraged this discovery to optimize a reporter assay to detect base editing levels as low as 0.01 %. Finally, we used this assay along with molecular dynamics simulations of full ABE:DNA complexes to better understand how the sequence recognition of mutant TadA variants change as they accumulate mutations to better edit DNA substrates.

Indexed as

Adenosine DeaminaseGene EditingCRISPR-Cas SystemsDNAMutationRNA, TransferAdenosine DeaminaseDNARNA, Transferadenosine deamination chemistrybase editingdirected evolutiongenome editingnucleic acids

Identifiers

PMID36947856
PMCPMC10514239
OpenAlexW4353032408

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.