Advanced peptide nanoparticles enable robust and efficient delivery of gene editors across cell types
Journal article, 2025
Efficient delivery of the CRISPR/Cas9 system and its larger derivatives, base editors, and prime editors remain a major challenge, particularly in tissue-specific stem cells and induced pluripotent stem cells (iPSCs). This study optimized a novel family of cell-penetrating peptides, hPep, to deliver gene-editing ribonucleoproteins. The hPep-based nanoparticles enable highly efficient and biocompatible delivery of Cre recombinase, Cas9, base-, and prime editors. Using base editors, robust and nearly complete genome editing was achieved in the human cells: HEK293T (96%), iPSCs (74%), and muscle stem cells (80%). This strategy opens promising avenues for ex vivo and, potentially, in vivo applications. Incorporating silica particles enhanced the system's versatility, facilitating cargo-agnostic delivery. Notably, the nanoparticles can be synthesized quickly on a benchtop and stored as lyophilized powder without compromising functionality. This represents an important advancement in the feasibility and scalability of gene-editing delivery technologies.
Cell-penetrating peptide (CPP)
Protein delivery
Diverse cells, including MuSC and iPSC
Base and primer editor
Gene editing
Synthetic gene editor delivery
Author
Oskar Gustafsson
Karolinska University Hospital
Karolinska Institutet
Supriya Krishna
The Max Delbrück Center for Molecular Medicine
Freie Universität Berlin
Sophia Borate
Karolinska Institutet
Marziyeh Ghaeidamini
Chalmers, Life Sciences, Chemical Biology
Xiuming Liang
Karolinska University Hospital
Karolinska Institutet
Osama Saher
Nile University
Karolinska University Hospital
Karolinska Institutet
Raul Cuellar
Karolinska Institutet
Karolinska University Hospital
Björn K. Birdsong
Royal Institute of Technology (KTH)
Samantha Roudi
Karolinska Institutet
Karolinska University Hospital
H. Yesid Estupiñán
Industrial University of Santander
Karolinska Institutet
Evren Alici
Karolinska Institutet
C. I. Edvard Smith
Karolinska University Hospital
Karolinska Institutet
Elin Esbjörner Winters
Chalmers, Life Sciences, Chemical Biology
Simone Spuler
The Max Delbrück Center for Molecular Medicine
Freie Universität Berlin
Olivier G. de Jong
Utrecht University
Helena Escobar
The Max Delbrück Center for Molecular Medicine
Joel Z. Nordin
Karolinska University Hospital
Karolinska Institutet
Samir El Andaloussi
Karolinska Institutet
Karolinska University Hospital
Journal of Controlled Release
0168-3659 (ISSN) 18734995 (eISSN)
Vol. 386 114038Subject Categories (SSIF 2025)
Cell and Molecular Biology
Medical Biotechnology
DOI
10.1016/j.jconrel.2025.114038
PubMed
40684990