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Published on: June 23, 2020
Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes
Gang Han1, Yao Zhang1, Li Zhong1
1State Key Laboratory of Experimental Hematology & The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics & International Joint Laboratory of Ocular Diseases (Ministry of Education), School of Medical Technology & School of Basic Medical Sciences, Tianjin Medical University, Qixiangtai Road, Heping District, 300070, Tianjin, China.
A novel Exosomal Anchor DNA Aptamer (EAA) enables efficient loading of nucleic acid drugs onto exosomes. This exosome-based delivery system shows promise for treating Duchenne Muscular Dystrophy and other genetic disorders.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Oligonucleotide therapeutics require advanced delivery systems for stability and targeted delivery.
- Exosomes are promising natural nanocarriers, but efficient loading methods are needed.
- Current exosome loading techniques are often inefficient or not generalizable.
Purpose of the Study:
- To develop a generalizable and efficient method for loading oligonucleotides onto exosomes.
- To evaluate the therapeutic potential of exosome-loaded nucleic acid drugs.
- To demonstrate the utility of the Exosomal Anchor DNA Aptamer (EAA) for exosome-based drug delivery.
Main Methods:
- SELEX (Systematic Evolution of Ligands by Exponential Enrichment) was used to identify an exosome-binding DNA aptamer (EAA).
- EAA was utilized to load nucleic acid drugs, including a thrombin inhibitor (NU172) and a phosphorodiamidate morpholino oligomer (PMO) for Duchenne Muscular Dystrophy (DMD).
- In vitro and in vivo studies in cell cultures and mdx mouse models were conducted to assess drug loading, stability, cellular uptake, tissue accumulation, and therapeutic efficacy.
Main Results:
- The identified EAA demonstrated high binding affinity to various exosomes, enabling efficient nucleic acid drug loading.
- Exosome-loaded NU172 showed improved serum stability and enhanced blood flow recovery post-injury.
- Exosome-loaded PMO (EXOEAA-PMO) significantly improved muscle cell uptake, tissue accumulation, and dystrophin expression in vitro and in vivo.
- Systemic administration of EXOEAA-PMO in mdx mice led to therapeutic levels of dystrophin restoration and functional recovery.
Conclusions:
- The Exosomal Anchor DNA Aptamer (EAA) provides an efficient and generalizable strategy for loading diverse nucleic acid drugs onto exosomes.
- Exosome-mediated delivery using EAA enhances the stability, targeting, and therapeutic efficacy of oligonucleotide drugs.
- This approach offers a promising platform for developing novel exosome-based nanotherapeutics for genetic diseases like Duchenne Muscular Dystrophy.
