Evidence map›Paper›PMID 42608275›Full record

ReviewTrends in biotechnology2026

On-target and off-target activities of CRISPR therapeutics across scales.

Merna Magdy, Justin R Gibson, Abishek Dhungana, Ashley Herring-Nicholas, Renee N Cottle, Eric A Josephs

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Trends in biotechnology, 2026. 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

6 authors.

Merna MagdyDepartment of Biomedical Engineering, College of Engineering and Applied Sciences (CEAS), Stony Brook University, The State University of New York (SUNY), Stony Brook, NY 11794, USA.
Justin R GibsonDepartment of Bioengineering, College of Engineering, Computing, and Applied Sciences, Clemson University, Clemson, SC 29634, USA; Clemson University Institute for Human Genetics, Clemson University, Greenwood, SC 29646, USA.
Abishek DhunganaDepartment of Bioengineering, College of Engineering, Computing, and Applied Sciences, Clemson University, Clemson, SC 29634, USA; Clemson University Institute for Human Genetics, Clemson University, Greenwood, SC 29646, USA.
Ashley Herring-NicholasDepartment of Nanoscience, The Joint School of Nanoscience and Nanoengineering (JSNN), The University of North Carolina at Greensboro, Greensboro, NC 27401, USA.
Renee N CottleDepartment of Bioengineering, College of Engineering, Computing, and Applied Sciences, Clemson University, Clemson, SC 29634, USA; Clemson University Institute for Human Genetics, Clemson University, Greenwood, SC 29646, USA. Electronic address: rcottle@clemson.edu.
Eric A JosephsDepartment of Biomedical Engineering, College of Engineering and Applied Sciences (CEAS), Stony Brook University, The State University of New York (SUNY), Stony Brook, NY 11794, USA; Department of Nanoscience, The Joint School of Nanoscience and Nanoengineering (JSNN), The University of North Carolina at Greensboro, Greensboro, NC 27401, USA. Electronic address: Eric.Josephs@stonybrook.edu.

Funding

Nonviral Delivery of CRISPR-Cas9 into Hepatocytes Combined with APAP Selection for Treatment of Familial HypercholesterolemiaR01HL168093 · NHLBI · CLEMSON UNIVERSITY · PI Renee Nicole Cottle · 2024 to 2026
$1.9M
Complex Mechanisms of Mutation and Mutation Avoidance in Living CellsR35GM133483 · NIGMS · UNIVERSITY OF NORTH CAROLINA GREENSBORO · PI JOSEPHS, ERIC ALAN · 2019 to 2023
$1.6M
A Molecular Grammar for Guide RNAs (gRNAs) with Engineered Secondary StructuresR21EB033595 · NIBIB · UNIVERSITY OF NORTH CAROLINA GREENSBORO · PI JOSEPHS, ERIC ALAN, MO, YIRONG · 2022 to 2023
$400k
NHLBI NIH HHS R01 HL168093NIBIB NIH HHS R21 EB033595NIGMS NIH HHS R35 GM133483
6 · The paper itself

Abstract

Recent FDA-approved gene-editing therapies illustrate not only the transformative potential of biotechnologies using CRISPR (clustered regularly interspaced short palindromic repeats)-derived ribonucleoproteins in treating a broad range of diseases but also the spectrum of possible molecular variations CRISPR therapeutics can adopt. These include exagamglogene autotemcel, an ex vivo therapy for hemoglobinopathies using CRISPR nuclease Cas9, and kayjayguran abengcemeran, an in vivo therapy using a protospacer adjacent motif-altered base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. In this opinion article, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing 'on-target' and 'off-target' mutational activities across the diverse contexts in which they occur.

Indexed as

Cas9inherited genetic diseaseN-of-1precision genetic medicine (PGM)specificity

Identifiers

PMID42608275
PMCPMC13509143

What OpenQuestion holds

Textmetadata
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.