Delivery approaches of immunomodulatory nucleic acids for cancer therapy

Messenger RNA (mRNA) vaccines have made remarkable public health contributions during the pandemic and initiated a new era for nucleic acid-based therapeutics. With the unique strength of nucleic acids, including not only mRNA but also DNA, microRNA, small interfering RNA (siRNA), and other nucleic acids, either in tuning off genes or introducing function, nucleic acid therapeutics have been regarded as potential candidates for the treatment of many different diseases, especially for the immunomodulation in cancer. However, the scope of the applications was limited by the challenges in delivery due to intrinsic properties of nucleic acids including low stability, immunogenicity, and toxicity. Bioengineering approaches toward efficient and targeted delivery of therapeutic nucleic acids have gained momentum in clinical applications in the past few decades. Recent advances in the biotechnological approaches for the delivery of mRNA, siRNA, and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas for immunomodulatory are promising alternatives in designing future cancer immunotherapy.