Exosome-based siRNA delivery targeting lincRNA-Cox2 for multiple sclerosis treatment
A novel therapeutic approach using exosomes to deliver siRNA targeting lincRNA-Cox2, a key regulator of neuroinflammation, to treat multiple sclerosis. This delivery platform aims to reduce disease severity, decrease neuroinflammation, and preserve myelin in affected individuals.
Overview
This research proposes an innovative exosome-based delivery platform for small interfering RNA (siRNA) targeting lincRNA-Cox2, a long non-coding RNA identified as a key driver of neuroinflammation and neuronal damage in multiple sclerosis (MS). By encapsulating siRNA within exosomes derived from bone marrow mesenchymal stem cells, the approach enables efficient transport of therapeutic molecules across biological barriers to reach the brain. The solution addresses a critical unmet need in MS treatment by targeting the underlying inflammatory pathways rather than only managing symptoms, with the potential to reduce disease severity, decrease neuroinflammation, and preserve myelin integrity.
Technical specifications
Core technology components:
- Exosome-based delivery system using extracellular vesicles isolated from mouse bone marrow mesenchymal stem cells, which have demonstrated capability to efficiently deliver small molecules into the brain
- siRNA payload specifically targeting lincRNA-Cox2, a validated mediator of neuroinflammation and neuronal damage in MS
- Super resolution microscopy validation to evaluate siRNA loading efficiency within exosomes using cy5-labeled tracking
- In vitro microglial cell testing to assess delivery efficiency in relevant neural cell types
- In vivo MS mouse model validation using the MOG-35-55-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice
Scientific basis:
- Prior studies have shown that knockdown of lincRNA-Cox2 via lentivirus attenuates neuroinflammation and EAE severity
- Previous work demonstrated that exosome-mediated siRNA delivery reduces LPS- and morphine-induced neuroinflammation in mice
Technology readiness level
The technology is currently at an early preclinical stage of development. The research team has established proof-of-concept evidence through prior studies showing that knockdown of lincRNA-Cox2 reduces neuroinflammation in mouse models. The proposed future validation plan includes four sequential steps: (1) isolation and characterization of exosomes from mesenchymal stem cells, (2) loading and efficiency evaluation of cy5-labeled siRNA into exosomes, (3) in vitro delivery efficiency testing in microglial cells, and (4) in vivo therapeutic efficacy evaluation in the MOG-35-55-induced MS mouse model. Successful completion of these studies would advance the technology toward IND-enabling studies and potential clinical translation for MS patients.
About University of Nebraska Medical Center
The University of Nebraska Medical Center is a public academic health sciences center in Omaha with a statewide footprint, uniting education, research, and patient care through an integrated hospital partnership. Co‑located clinical and research facilities provide access to patients, data, and specimens, while shared cores, advanced simulation, and centralized clinical trial support speed translation. A regional care network across Nebraska and the central U.S. provides recruitment and real‑world deployment sites, and Omaha’s health and biotech ecosystem eases collaboration and scale‑up. Research is backed by the National Institutes of Health and other U.S. agencies, and a dedicated tech transfer office manages IP, licensing, startups, and industry‑sponsored agreements.
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