ArticleNature medicine2018
A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 491 papers.
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Who cites it
491 citing papers in PubMed, 782 citations in OpenAlex.
- Nucleofection-Based CRISPR/Cas Delivery in Human T Cells for Immunotherapy Applications.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Translating base editors: a decade of progress from the bench to the clinic.Nature reviews. Drug discovery · 2026Review
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- CRISPR-Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off-Target Effects for Clinical Translation.Health science reports · 2026Article
- Unlocking the curative potential of gene transfer and editing for hematopoietic disorders.Experimental hematology · 2026Review
- CCR5 as a Therapeutic Target in HIV Disease: From CRISPR/Cas9 Gene Editing to Maraviroc-Mediated Inhibition.Viruses · 2026Review
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- From Design to Single-Cell Cloning: A Complete RNP-Based CRISPR-Cas9 Protocol for Precision Gene Correction in Human iPSCs.Stem cell reviews and reports · 2026Article
- SLC25A38 gene modification mediated by CRISPR/Cas9 in HEK293T cell line.Journal of applied genetics · 2026Article
- CRISPR application in hematological disorders: from bench to bedside.Blood advances · 2026Review
- UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.Nature communications · 2026Article
- Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2.Nature communications · 2026Article
- CRISPR RNA architecture steers Cas9 catalysis and fidelity via a guide repeat clasp motif.Nucleic acids research · 2026Article
- Identification and structure determination of a type III-Bv CRISPR complex that post-translationally modifies an associated toxin.Structure (London, England : 1993) · 2026Article
- Article
- Chemical and Structural Engineering of Guide RNAs for Precision Genome Editing: From Design Principles to Clinical Applications.Chemical biology & drug design · 2026Review
- CRISPR integration of an FLT3 CAR into the TRAC locus generates CAR T cells for AML.Genome medicine · 2026Article
- Beyond Permanent Genome Editing: Molecular Delivery Strategies for RNA Editing and Epigenome-Editing Therapeutics.International journal of molecular sciences · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
431 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Translation of the CRISPR-Cas9 system to human therapeutics holds high promise. However, specificity remains a concern especially when modifying stem cell populations. We show that existing rationally engineered Cas9 high-fidelity variants have reduced on-target activity when using the therapeutically relevant ribonucleoprotein (RNP) delivery method. Therefore, we devised an unbiased bacterial screen to isolate variants that retain activity in the RNP format. Introduction of a single point mutation, p.R691A, in Cas9 (high-fidelity (HiFi) Cas9) retained the high on-target activity of Cas9 while reducing off-target editing. HiFi Cas9 induces robust AAV6-mediated gene targeting at five therapeutically relevant loci (HBB, IL2RG, CCR5, HEXB, and TRAC) in human CD34
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Registered trials
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.