Advanced nanobiomed researchMay 6, 2026

Delivering Gene-Editing Tools and Long DNA into Primary Blood Cells Using Gold Nanoparticles Without Viruses

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

A synthetic gold nanoparticle system delivered Cas9 protein complexes and long DNA templates into primary blood cells to enable transgene insertion.

Evidence

This preclinical proof-of-concept study tested modified gold nanoparticles carrying CRISPR-Cas9 ribonucleoprotein and up to 2.1 kb donor DNA in primary human T cells and hematopoietic stem and progenitor cells at two gene targets.

Caveat

The results are limited to ex vivo cell-engineering experiments, so in vivo efficacy and therapeutic performance were not shown.

Simplified

Gene editing using CRISPR systems has gained traction for its potential to treat various diseases, but delivery remains a major challenge. We have previously reported an entirely synthetic gold nanoparticle formulation which can safely and effectively deliver multiple different CRISPR systems as ribonucleoprotein (RNP) into hematopoietic stem cells and immune cells. Here, we describe a modified version of this nanoparticle to simultaneously deliver CRISPR Cas9 RNP and transgene-encoding DNA templates (HDT) as long as ~2.1 kb. We evaluate this HDT-CRISPR-AuNP for gene editing at two loci of interest with different transgene cargo. These nanoparticles successfully deliver gene editing into primary human T cells and hematopoietic stem and progenitor cells with insertion of an antigen-specific T cell receptor transgene. This proof-of-concept immune engineering study demonstrates a simple, synthetic nanoformulation for co-delivery of all cargo required for CRISPR-mediated delivery of transgene cassettes with potential for efficacy in vivo.