Triggering RNAi with multifunctional RNA nanoparticles and their delivery

Bich Ngoc Dao, Mathias Viard, Angelica N. Martins, Wojciech K. Kasprzak, Bruce A. Shapiro, and Kirill A. Afonin
  • 1 Department of Chemistry, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, North Carolina 28223, USA
  • 2 Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA
  • 3 Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, Maryland, USA
  • 4 Department of Biology, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, North Carolina 28223, USA
  • 5 Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA
  • 6 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA

Abstract

Proteins are considered to be the key players in structure, function, and metabolic regulation of our bodies. The mechanisms used in conventional therapies often rely on inhibition of proteins with small molecules, but another promising method to treat disease is by targeting the corresponding mRNAs. In 1998, Craig Mellow and Andrew Fire discovered dsRNA-mediated gene silencing via RNA interference or RNAi. This discovery introduced almost unlimited possibilities for new gene silencing methods, thus opening new doors to clinical medicine. RNAi is a biological process that inhibits gene expression by targeting the mRNA. RNAi-based therapeutics have several potential advantages (i) a priori ability to target any gene, (ii) relatively simple design process, (iii) sitespecificity, (iv) potency, and (v) a potentially safe and selective knockdown of the targeted cells. However, the problem lies within the formulation and delivery of RNAi therapeutics including rapid excretion, instability in the bloodstream, poor cellular uptake, and inefficient intracellular release. In an attempt to solve these issues, different types of RNAi therapeutic delivery strategies including multifunctional RNA nanoparticles are being developed. In this mini-review, we will briefly describe some of the current approaches.

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