Evidence map›Paper›PMID 39345554›Full record

ArticlebioRxiv : the preprint server for biology2024

Tailoring a CRISPR/Cas-based Epigenome Editor for Programmable Chromatin Acylation and Decreased Cytotoxicity.

Jacob Goell, Jing Li, Barun Mahata, Alex J Ma, Sunghwan Kim, Spencer Shah, Shriya Shah, Maria Contreras, Suchir Misra, Daniel Reed and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Jacob GoellDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.ORCID 0000-0002-6554-8769
Jing LiDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Barun MahataDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Alex J MaDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Sunghwan KimDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Spencer ShahDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Shriya ShahDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Maria ContrerasDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Suchir MisraDepartment of Biosciences, Rice University, Houston, TX 77030, USA.
Daniel ReedDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Guy C BedfordDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Mario EscobarDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.
Isaac B HiltonDepartment of Bioengineering, Rice University, Houston, TX 77030, USA.ORCID 0000-0002-3064-8532

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
VISION RESEARCH CENTERP30EY002520 · NEI · BAYLOR COLLEGE OF MEDICINE · PI Samuel M Wu · 1985 to 2026
$14.8M
Site-specific control of human gene regulation for therapeutically applicable mechanistic insights (R35GM143532)R35GM143532 · NIGMS · RICE UNIVERSITY · PI HILTON, ISAAC · 2021 to 2025
$1.9M
High Throughput Genomic Sequencer at BCM Core FacilityS10OD023469 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2017 to 2017
$600k
Programmable control over histone acetylation at human regulatory elements using precision epigenome editingR56HG012206 · NHGRI · RICE UNIVERSITY · PI HILTON, ISAAC · 2022 to 2022
$569k
Acquisition of the Fluidigm system to accelerate functional genomics researchS10OD018033 · OD · BAYLOR COLLEGE OF MEDICINE · PI CHEN, RUI · 2014 to 2014
$396k
Acquisition of 10X Genomics Chromium Instrument to Accelerate Genomic and Single Cell Transcriptomic ResearchS10OD025240 · OD · BAYLOR COLLEGE OF MEDICINE · PI DODDAPANENI, HARSHA VARDHAN · 2018 to 2018
$125k
American Heart Association-American Stroke Association 917025NCI NIH HHS P30 CA125123NEI NIH HHS P30 EY002520NHGRI NIH HHS R56 HG012206NIGMS NIH HHS R35 GM143532NIH HHS S10 OD018033NIH HHS S10 OD023469NIH HHS S10 OD025240
6 · The paper itself

Abstract

Engineering histone acylation states can inform mechanistic epigenetics and catalyze therapeutic epigenome editing opportunities. Here, we developed engineered lysine acyltransferases that enable the programmable deposition of acetylation and longer-chain acylations. We show that targeting an engineered lysine crotonyltransferase results in weak levels of endogenous enhancer activation yet retains potency when targeted to promoters. We further identify a single mutation within the catalytic core of human p300 that preserves enzymatic activity while substantially reducing cytotoxicity, enabling improved viral delivery. We leveraged these capabilities to perform single-cell CRISPR activation screening and map enhancers to the genes they regulate

Indexed as

CRISPRCRISPRaenhancerEP300Epigenome editinghistone acetylationhistone crotonylationoff-target editingPerturb-seqprotein engineering

Identifiers

PMID39345554
PMCPMC11429961

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.