Extracellular vesicle-based nucleic acid delivery

Extracellular vesicles (EVs) are a heterogeneous class of natural vesicles that facilitate intercellular communication by functional transfer of lipids and biomolecular cargoes, such as miRNAs, mRNAs and proteins. As a naturally occurring delivery vehicle for nucleic acids, EVs are characterized by multiple advantageous characteristics, such as unique size and structure, excellent biocompatibility, immunologically inert, increased stability in circulation, intrinsic targeting capacity and the capability of membrane fusion and crossing biological barriers. Of note, the delivery properties of EVs can be further improved by genetic engineering of donor cells or direct modification of EVs. Over the last decade, EVs have sparkled intensive interest for delivery of small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). In recent years, increasing attention has been focused on exploring a variety of strategies to harness EVs for delivery of more nucleic acid types. In the present perspective, we provide a capsule overview of the latest accomplishments and trends in the field of EV-based delivery systems for siRNAs, miRNAs, messenger RNAs (mRNAs), clustered regularly interspaced short palindromic repeats-associated endonuclease (CRISPR/Cas) systems, antisense oligonucleotides (ASOs), circular RNA (circRNAs), long noncoding RNAs (lncRNAs) and DNAs. This perspective may offer insights into the rational design of more cutting-edge extracellular vesicle-based nucleic acid delivery nanoplatforms.