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Published on: July 23, 2016
Aminophosphonate-Derived Lipid Nanoparticles Enable Circular RNA Delivery for Functional Recovery after Spinal Cord
Haoyuan Li1,2, Yuebao Zhang3,4,2, Yichen Zhong1
1Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States.
Researchers developed a novel biomimetic lipid nanoparticle system (CROSS) for spinal cord injury (SCI) treatment. This innovative delivery system effectively restored motor and bladder function in an SCI model.
Area of Science:
- Biomaterials Science
- Neuroscience
- Drug Delivery Systems
Background:
- Spinal cord injury (SCI) is a severe neurological condition with limited treatment options.
- Current treatments lack comprehensive strategies for neural repair, including neuroprotection and neurogenesis.
- Developing effective delivery systems is crucial for advancing SCI therapeutics.
Purpose of the Study:
- To create novel biomimetic ionizable lipids for enhanced mRNA and circular RNA delivery.
- To formulate these lipids into lipid nanoparticles (LNPs) for efficient neural delivery.
- To evaluate a new delivery system for treating spinal cord injury.
Main Methods:
- Synthesized a library of biomimetic aminophosphate, aminophosphoramidate, and aminophosphonate (AP) lipids.
- Formulated AP lipids into lipid nanoparticles (LNPs) for mRNA delivery in neuronal cells.
- Developed a two-step method for circular RNA production and combined it with AP LNPs into the CROSS system.
- Administered CROSS loaded with specific circular RNAs (Sox2, Ascl1, GDNF) in a spinal cord injury model.
Main Results:
- AP60 LNP demonstrated superior mRNA delivery efficiency compared to the FDA-approved MC3 LNP.
- The developed CROSS system efficiently delivered circular RNA for sustained protein expression.
- Local and intravenous administration of CROSS in an SCI model led to significant motor function recovery and restored bladder function.
Conclusions:
- The novel CROSS platform, utilizing biomimetic aminophosphonate-derived lipids nanoparticles, offers a promising strategy for spinal cord injury treatment.
- This innovative delivery system facilitates efficient delivery of therapeutic RNAs for neural repair.
- The study highlights the potential of CROSS in restoring both motor and autonomic functions after SCI.
