Precision chemical engineering of dendrimers for nucleic acid delivery

Nucleic acid therapeutics, including oligonucleotides, messenger RNA and DNA, are promising drug modalities for treating various diseases. However, despite their increasing impact on medicine, their precise and efficient delivery remains a considerable challenge. Dendrimers, recognized by their uniquely branched architecture and precise structures in concert with cooperative multivalency, are a platform for targeted and precise delivery of nucleic acid therapeutics. Here we review state-of-the-art engineering of dendrimers pertaining to nucleic acid delivery, highlighting progress made in their design and functional mechanization for delivering different types of nucleic acids for therapeutic applications. We also discuss challenges including manufacturing, safety and regulatory issues associated with their clinical applications. Finally, we conclude by offering our perspective on dendrimer engineering that are expected to overcome current obstacles for advancing nucleic acid therapeutics development.