Skip to content
Log in
Sponsored Artificial Intelligence: A Modern Approach, Global Edition Artificial Intelligence: A Modern Approach, Global Edition

Efficient and precise programmable DNA knock-in without double-strand breaks

Yanmin Gao Yu Ma Ke-Xin Yu Yin-Tian Liu Buming Gu Hao Tang Wen-Jie Yan Shuang-Shuang Yang Jin-Hao Su Xin-Dong Wang Xin Ma Xin-Ming Wang Fang Wang Qingyang Li Meng-Ying Liu Haifeng Wang
Jul 2026 · Nature · Vol 657, pp. 284 - 294 · 0 citations · 83 references
Medicine

TL;DR

Kilobase-scale nickase-targeting (KNIT) editing enables single-nick-based DNA insertion across genomic loci and cell types, supporting insertion of DNA fragments exceeding 10 kb, with high efficiency and minimal unwanted off-target effects.

DOI PubMed Semantic Scholar
View source

Similar papers

Aug 2026

Next-Generation Genome Editing: Overcoming CRISPR-Cas9 Limitations with Prime Editing and PASTE Technology

CRISPR-Cas9 has transformed gene editing; however, it is based on doublestrand DNA breaks, which may result in unintentional mutations and structural alterations, thereby limiting its clinical translation. Instead of DSBs, new precision instruments, including prime editing, can be used to perform accurate search-and-replace DNA editing with a Cas9 nickase and reverse transcriptase. Prime editing can perform all base substitutions and small edits with improved precision and reduced off-target activity, which has promising results in disease modelling with patient-derived organoids. Nonetheless, it is cumbersome, inefficient, and thus hard to deliver. This is improved by the Programmable Addition via Site-specific Targeting Elements system, which uses Prime editing in combination with serine integrases to insert large DNA sequences with no gaps to provide lasting gene replacement and maintain natural gene regulation. Emerging delivery options, including lipid nanoparticles, dual adeno-associated virus systems, and virus-like particles, allow the delivery to be transient and tissue-targeted, which minimizes the risks over the long-term. Early clinical translation efforts are currently underway, with the first FDA-approved trial of one Prime editing-based therapy, but it has been struggling with efficiency, safety, and delivery. Future success will depend on predictive machinelearning devices and strictly controlled editing systems. Genome engineering is evolving from a DNA-cutting system to a precise and programmable genome editing system, which may support the future development of safer and more precise therapeutic strategies.

Vikash Kumar, Aman Kumar, Balak Das Kurmi · 0 citations
#gene editing Aug 2026

Engineering RNA-guided bridge recombinases for precise large-scale genome editing.

An RNA-guided bridge recombinase system is engineered through rational mutagenesis and AI-assisted directed evolution, enabling programmable chromosomal rearrangements in both plant and mammalian cells and achieving up to a 29.8-fold increase in activity.

Rui Gao, Jingjing Wei, Chao Sun et al. · 0 citations
Jul 2026

Repurposing base editors for targeted knock-in and simultaneous multiplex knockouts to generate allo-CAR T cells with minimal translocations.

Compared with multiplex Cas9 editing, BEKI markedly reduced chromosomal translocations while preserving cell viability, and provides a streamlined and scalable strategy for multiplex CAR T-cell engineering with improved genomic stability, advancing safer next-generation cell therapies for cancer and autoimmune diseases.

Glaser Viktor, Becker Lily Jo, Fuster-García Carla et al. · 0 citations
Review 2026

From Double-Strand Breaks to Precision Edits: A Comparative Review of Modern Genome Editing Tools

This review compares Cas9-mediated homology-directed repair (HDR) with generations of cytosine base editors (CBE1–CBE3), adenine base editors (ABE1-ABE7), and prime editors (PE1–PE3b), focusing on their mechanistic distinctions, efficiencies, delivery challenges, and therapeutic applications.

Anoushka Sinha · 0 citations
#gene editing Open access Aug 2026

Precise genomic integration of large DNA fragments by donor-directed annealing using prime editing.

A programmable gene replacement tool, named prime assembly (PA), which adapts prime editors to produce one or two pairs of 3'-flaps on both the genome and donor DNA, allowing megabase-scale genomic excision and/or kilobase-scale donor insertion at the gene of interest.

Hojun Jung, Bada Jeong, Yong-Woo Kim et al. · 1 citation

We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.