Single-vector AAV delivery of En-ISPmu1 and donor DNA for in vivo targeted genome integration

TnpBs are compact RNA-guided nucleases ideally suited for in vivo delivery. By screening novel TnpBs identified from large metagenomic datasets, ISPmu1 was discovered and its protein and ωRNA were engineered to generate En-ISPmu1, which achieved editing efficiencies exceeding 65% across 12 human loci. Owing to its compact size, En-ISPmu1 was delivered together with a donor DNA in a single AAV vector, yielding up to 12.7% targeted integration in mouse liver. These findings establish En-ISPmu1 as a promising versatile platform for in vivo therapeutic genome editing applications.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-28
DOI
https://doi.org/10.64898/2026.10.26.761871
Primary Topic
CRISPR and Genetic Engineering
Type
preprint

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preprint

Single-vector AAV delivery of En-ISPmu1 and donor DNA for in vivo targeted genome integration

Federica Esposito, Alberto Auricchio, Fanny Collaud, Giuseppe Ronzitti et al.
1 links
bioRxiv (Cold Spring Harbor Laboratory)
CRISPR and Genetic Engineering
preprint

Single-vector AAV delivery of En-ISPmu1 and donor DNA for in vivo targeted genome integration

Federica Esposito, Alberto Auricchio, Fanny Collaud, Giuseppe Ronzitti, Nicola Segata, Matteo Ciciani, Pasquale Piccolo, Anna Cereseto, Ilaria Bonuzzi, Alessio Conci
preprint en

Abstract

TnpBs are compact RNA-guided nucleases ideally suited for in vivo delivery. By screening novel TnpBs identified from large metagenomic datasets, ISPmu1 was discovered and its protein and ωRNA were engineered to generate En-ISPmu1, which achieved editing efficiencies exceeding 65% across 12 human loci. Owing to its compact size, En-ISPmu1 was delivered together with a donor DNA in a single AAV vector, yielding up to 12.7% targeted integration in mouse liver. These findings establish En-ISPmu1 as a promising versatile platform for in vivo therapeutic genome editing applications.

bioRxiv (Cold Spring Harbor Laboratory)
Inserm (FR), University of Trento (IT), Université Paris-Saclay (FR), Genethon (France) (FR), Telethon Institute Of Genetics And Medicine (IT), Université d'Évry Val-d'Essonne (FR)
Università degli Studi di Trento, HORIZON EUROPE Framework Programme
Good health and well-being
CRISPR and Genetic Engineering
DOIOpen Access PDFOpenAlex
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Single-vector AAV delivery of En-ISPmu1 and donor DNA for in vivo targeted genome integration — Federica Esposito, Alberto Auricchio, et al. · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS