Science advancesSep 26, 2025

Strengthened plant-based lipid nanoparticles for targeted gene regulation in colon diseases

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

An oral plant-derived lipid nanoparticle platform may deliver CRISPR ribonucleoproteins for macrophage epigenome editing in colonic disease models.

Evidence

A formulation and preclinical model study tested TPGS-reinforced mulberry leaf LNPs, reporting 59.7% macrophage editing versus 43.0% with CRISPRMAX and improved colitis-associated outcomes.

Caveat

The abstract reports platform and preclinical disease effects, not human clinical efficacy or safety.

Simplified

The clinical application of CRISPR-Cas9 remains limited by delivery challenges, particularly for oral administration. Lysine-specific demethylase 1 () plays a key role in colonic inflammation and tumorigenesis. Here, we developed an oral genome-editing platform (TPGS-RNP@LNP), where-targeting ribonucleoproteins (RNPs) were encapsulated in mulberry leaf lipid nanoparticles (LNPs) and formulated with d-α-tocopherol polyethylene glycol succinate (TPGS). TPGS reinforced the lipid bilayer of LNPs, enhanced gastrointestinal stability, and facilitated colonic mucus penetration. Upon the galactose receptor-mediated endocytosis of TPGS-RNP@LNPs by macrophages, their fusion with the endosomal membrane and the presence of nuclear localization signals ensured the nuclear delivery of RNPs. TPGS-RNP@LNPs achieved 59.7%editing efficiency in macrophages, surpassing the commercial CRISPRMAX (43.0%). Oral TPGS-RNP@LNPs promoted H3K4 methylation to modulate epigenetic states, achieving inflammation mitigation, epithelial barrier restoration, and retardation of colitis and its associated tumorigenesis. As an LNP-based oral RNP delivery system, TPGS-RNP@LNPs provide a promising platform for precise treatment of colorectal diseases. Lsd1Lsd1Lsd1