Extracellular vesicle-based delivery systems for nucleic acid therapeutics

Area of Science:

• Biotechnology
• Drug Delivery Systems
• Molecular Therapeutics

Background:

• Nucleic acid therapeutics show promise but face delivery challenges including nuclease degradation and poor cellular uptake.
• Approved nucleic acid drugs highlight the therapeutic potential, yet clinical translation remains limited by delivery hurdles.
• Extracellular vesicles (EVs) are natural nanoscale carriers with potential for safe and targeted nucleic acid delivery.

Purpose of the Study:

• To review current methods and recent advancements in extracellular vesicle (EV) preparation and nucleic acid loading.
• To explore various administration routes for nucleic acid-loaded EVs, including intravenous, local, oral, intranasal, and inhalation.
• To provide guidance for the optimal design and clinical application of nucleic acid-loaded EVs.

Main Methods:

• Summarizing classical and novel techniques for EV isolation and characterization.
• Detailing strategies for loading diverse nucleic acids (e.g., mRNA, siRNA) into EVs.
• Compiling and analyzing data on different administration routes for EV-based therapies.

Main Results:

• EVs provide a safe, efficient, targeted, and non-pathogenic platform for nucleic acid delivery.
• Established methods for EV preparation and nucleic acid loading are discussed, alongside emerging techniques.
• Multiple administration routes demonstrate feasibility for EV-mediated therapeutic delivery.

Conclusions:

• Nucleic acid-loaded EVs represent a significant advancement in drug delivery, addressing key limitations of traditional nucleic acid therapeutics.
• Further research into EV preparation, loading optimization, and administration strategies will facilitate clinical translation.
• This review serves as a guide for developing effective EV-based nucleic acid therapies.