Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA...

Area of Science:

• Regenerative Medicine
• Neuroscience
• Biotechnology

Background:

• Efficient in vivo delivery of therapeutic proteins for spinal cord injury (SCI) remains a significant challenge.
• Nucleoside-modified messenger RNA (mRNA) presents a promising platform for safe and effective protein delivery.

Purpose of the Study:

• To investigate the potential of lipid nanoparticle (LNP)-encapsulated human interleukin-10 (hIL-10)-encoding nucleoside-modified mRNA for SCI treatment.
• To evaluate the neuroprotective effects and functional recovery induced by hIL-10 mRNA-LNP in a rat SCI model.

Main Methods:

• Rats with spinal cord contusion injuries received intralesional administration of hIL-10 mRNA-LNP.
• Assessment of microglia/macrophage reaction, functional recovery, and expression of specific tissue factors post-treatment.

Main Results:

• hIL-10 mRNA-LNP treatment significantly reduced microglia/macrophage response in the injured spinal cord segment.
• Significant functional recovery was observed in rats treated with hIL-10 mRNA-LNP compared to control groups.
• Increased expression of tissue inhibitor of metalloproteinase 1 and ciliary neurotrophic factor was noted 5 days post-injection, indicating a delayed secondary effect.

Conclusions:

• Nucleoside-modified mRNA encoding neuroprotective factors, such as hIL-10, is an effective strategy for promoting spinal cord injury repair.
• This mRNA-LNP approach holds potential for modulating the injured spinal cord microenvironment and enhancing neuroprotection.
• The findings support the development of mRNA-based therapeutics for neurological disorders and tissue regeneration.