Evidence map›Paper›PMID 41536070›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Precision A3G base editors for disease modeling and correction.

Hongzhi Zeng, Aidi Liu, Tyler C Daniel, Devin A Golla, Zhenyu Lu, Rebecca Serodio, Brigid A Millette, Ananya Lingineni, Peretz Gilberd, Kelly Chee and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

15 authors.

Hongzhi ZengDepartment of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA.
Aidi LiuDepartment of Bioengineering, Rice University, Houston, TX 77005, USA.
Tyler C DanielDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA.
Devin A GollaDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhenyu LuCenter for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Master of Biotechnology Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rebecca SerodioDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA.
Brigid A MilletteCenter for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ananya LingineniDepartment of Bioengineering, Rice University, Houston, TX 77005, USA.
Peretz GilberdDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Kelly CheeDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Komal TallooDepartment of Bioengineering, Rice University, Houston, TX 77005, USA.
Advaith PeddiDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
So Hyun ParkDepartment of Bioengineering, Rice University, Houston, TX 77005, USA.
Gang BaoDepartment of Bioengineering, Rice University, Houston, TX 77005, USA. Electronic address: gang.bao@rice.edu.
Xue GaoDepartment of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA; Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: xuegao@seas.upenn.edu.

Funding

Training Program in Neuroengineering and MedicineT32NS091006 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Brian Litt · 2015 to 2026
$4.1M
Deciphering unintended large gene modifications in gene editing for sickle cell diseaseR01HL169761 · NHLBI · RICE UNIVERSITY · PI Gang Bao · 2023 to 2026
$2.7M
Develop High-Precision and Multiplex Base Editing Approaches for Therapeutic ApplicationsR01HL157714 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI GAO, XUE · 2021 to 2024
$2.0M
Chemically inducible split base editors for precise and controllable in vivo genome editingR01HL173243 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Xue Gao, Zheng Sun · 2025 to 2026
$1.3M
NHLBI NIH HHS R01 HL157714NHLBI NIH HHS R01 HL169761NHLBI NIH HHS R01 HL173243NINDS NIH HHS T32 NS091006
6 · The paper itself

Abstract

Cytosine base editors (CBEs) enable efficient cytosine-to-thymine substitutions at targeted genomic loci without introducing double-stranded breaks. Among CBEs, APOBEC3G BEs (A3G-BEs) preferentially edit the second cytosine within a 5'-CC-3' motif in human cells, reducing potential bystander editing. However, A3G-BEs often unintentionally edit multiple CC motifs within their editing window and are limited by protospacer adjacent motif (PAM) constraints imposed by SpCas9, which restricts their applicability. Here, we engineered A3G-BE variants through linker optimization, rational mutagenesis, and the integration of SpG and SpRY Cas9 effectors with relaxed PAM constraints. These improvements enhanced the precision of single-cytosine editing within CC motifs and broadened the targeting scope to previously inaccessible genomic sites. We then validated the engineered A3G-BE variants by precisely installing and correcting cystic fibrosis-causing mutations in HEK293T cells. When applied to 16HBE14o-human bronchial epithelial cells, precise editing modulated cystic fibrosis transmembrane conductance regulator mRNA levels, protein expression, and channel function, establishing precision A3G-BE variants as powerful tools for modeling and treating cystic fibrosis and other human diseases.

Indexed as

APOBEC-3G DeaminaseCystic FibrosisGene EditingCRISPR-Cas SystemsCystic Fibrosis Transmembrane Conductance RegulatorHEK293 CellsHumansMutationAPOBEC-3G DeaminaseAPOBEC3G protein, humanCystic Fibrosis Transmembrane Conductance RegulatorAPOBEC3Gbase editingCRISPR-Cas9cystic fibrosisgene editinghuman bronchial epithelial cellsprotein engineeringreduced bystander editing

Identifiers

PMID41536070
PMCPMC12934557

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.