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Auto-SMART web platform automates repair-template design for CRISPR/Cas9 homology-directed editing

A preprint describes a freely accessible web tool that automates the design of repair templates for CRISPR/Cas9 homology-directed editing, expanding the usable guide-RNA space by exploiting silent mutations between cut site and intended edit.

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A preprint posted to bioRxiv introduces Auto-SMART, a web-based platform that automates the design of repair templates for CRISPR/Cas9 homology-directed repair (HDR). A persistent practical constraint in precision genome editing is that the efficiency of HDR depends partly on the proximity of the guide-RNA cut site to the intended edit: when these are far apart, editing efficiency drops substantially. The SMART strategy (Silently Mutate And Repair Template) addresses this by introducing silent (synonymous) mutations in the sequence between the Cas9 cut and the desired edit, preserving the encoded protein sequence whilst expanding the range of usable guide RNAs.

Designing SMART repair templates manually is laborious and requires specialist knowledge. Auto-SMART implements this process as an automated web interface, accepting a target sequence and desired edit as inputs and returning optimised repair-template designs with expanded guide-RNA options. The authors describe the tool as applicable to both basic research applications and the early stages of gene therapy development.

The preprint has not yet been peer reviewed. The tool addresses a recognised bottleneck in genome engineering workflows and may be of immediate practical use to researchers designing HDR experiments across model organisms and human cell systems. Details of the web platform's availability are described in the preprint.

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  1. Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-09-24
    Auto-SMART: a web-based platform for repair-template design for CRISPR/Cas9 homology-directed editing

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crispr homology-directed-repair genome-editing repair-template guide-rna-design gene-therapy web-tool preprint
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