Materials today (Kidlington, England)Oct 31, 2025

Special lipid nanoparticles help deliver circular RNA to improve recovery after spinal cord injury

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

An aminophosphonate-derived lipid nanoparticle platform delivered circular RNAs and improved functional recovery in spinal cord injury models.

Evidence

This platform and preclinical therapy experiment screened AP lipid nanoparticles in neurons and astrocytes, built the CROSS circular RNA system, and tested local and intravenous circular Sox2, Ascl1, and GDNF RNA delivery in an SCI model.

Caveat

The abstract does not specify the animal model details, sample size, durability, or safety profile beyond functional recovery endpoints.

Simplified

Spinal cord injury (SCI) is a devastating neurological disorder that results in severe disability and imposes a high social and economic burden. Effective recovery from SCI requires comprehensive neural repair strategies, including neurogenesis and neuroprotection. Inspired by the structure of phospholipids in nature, we developed a library of biomimetic ionizable lipids, containing aminophosphate, aminophosphoramidate, or aminophosphonate groups (AP lipids). Then, we formulated these AP lipids into lipid nanoparticles (LNPs) and examined their mRNA delivery efficiency in neurons and astrocytes. Among these AP LNPs, AP60 LNP showed superior delivery efficiency compared to FDA approved D-Lin-MC3-DMA (MC3) LNP. To achieve longer protein expression, the circular RNA was used in LNPs. Additionally, we developed a two-step method for circular RNA production, providing a simple yet highly efficient approach. By combining these innovations, a circular RNA loaded aminophosphonate-derived lipids nanoparticles delivery system (CROSS) was constructed. To explore a therapeutic regimen, CROSS-loaded with circular Sox2, Ascl1, and GDNF RNAs were administered locally and intravenously in SCI model, which led to the restoration of bladder function and significant motor function recovery. In summary, the CROSS platform provided a novel and effective strategy for treating SCI.