4.6 Review

Strategies to deliver RNA by nanoparticles for therapeutic potential

Journal

MOLECULAR ASPECTS OF MEDICINE
Volume 83, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.mam.2021.100991

Keywords

RNA therapy; Drug delivery; Nanomedicine; Endosomal escape; Targeting; Cellular uptake

Funding

  1. University of Southern California, NIH Director's New Innovator Award [DP2-DK121328]
  2. NSF EAGER [DMR BMAT 2132744]
  3. PKD Foundation [839636]
  4. WISE Major Support Award

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The use of various types of RNA molecules for prevention and therapy of pathologies has shown great potential. However, limitations such as short in vivo half-life, lack of targeted delivery, and safety issues have hindered the therapeutic efficacy. Nanoparticle-mediated delivery has been successful in overcoming these limitations, with multiple formulations already in clinical trials and approved by FDA. This review summarizes the methods of modifying nanoparticles for optimal therapeutic effects in RNA delivery.
The use of a variety of RNA molecules, including messenger RNA, small interfering RNA, and microRNA, has shown great potential for prevention and therapy of many pathologies. However, this therapeutic promise has historically been limited by short in vivo half-life, lack of targeted delivery, and safety issues. Nanoparticle (NP)mediated delivery has been a successful platform to overcome these limitations, with multiple formulations already in clinical trials and approved by the FDA. Although there is a diversity of NPs in terms of material formulation, size, shape, and charge that have been proposed for biomedical applications, specific modifications are required to facilitate sufficient RNA delivery and adequate therapeutic effect. This includes optimization of (i) RNA incorporation into NPs, (ii) specific cell targeting, (iii) cellular uptake and (iv) endosomal escape ability. In this review, we summarize the methods by which NPs can be modified for RNA delivery to achieve optimal therapeutic effects.

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