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Delivery of RNAi-Based Therapeutics for Bone Regeneration

  • Regenerative Biology and Medicine in Osteoporosis (S Bryant and M Krebs, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The clinical significance, target pathways, recent successes, and challenges that preclude translation of RNAi bone regenerative approaches are overviewed.

Recent Findings

RNA interference (RNAi) is a promising new therapeutic approach for bone regeneration by stimulating or inhibiting critical signaling pathways. However, RNAi suffers from significant delivery challenges. These challenges include avoiding nuclease degradation, achieving bone tissue targeting, and reaching the cytoplasm for mRNA inhibition. Many drug delivery systems have overcome stability and intracellular localization challenges but suffer from protein adsorption that results in clearance of up to 99% of injected dosages, thus severely limiting drug delivery efficacy.

Summary

While RNAi has myriad promising attributes for use in bone regenerative applications, delivery challenges continue to plague translation. Thus, a focus on drug delivery system development is critical to provide greater delivery efficiency and bone targeting to reap the promise of RNAi.

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Acknowledgements

The authors would like to thank Marian Ackun-Farmmer for helpful discussions in the development and editing of the manuscript.

Funding

The National Science Foundation (NSF) DMR1206219, CBET1450987, and DGE1419118; National Institutes of Health (NIH) R01 AR064200, R01 AR056696, R01 DE018023, F31 AR076874; and New York State Stem Cell Science (NYSTEM) N11G-035 provided funding for this study.

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Author notes

  1. Dominic W. Malcolm and Yuchen Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Rochester, 308 Robert B. Goergen Hall, Rochester, NY, 14627, USA

    Dominic W. Malcolm, Yuchen Wang, Clyde Overby, Maureen Newman & Danielle S. W. Benoit

  2. Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA

    Dominic W. Malcolm, Yuchen Wang, Clyde Overby, Maureen Newman & Danielle S. W. Benoit

  3. Materials Science Program, University of Rochester, Rochester, NY, USA

    Danielle S. W. Benoit

  4. Department of Chemical Engineering, University of Rochester, Rochester, NY, USA

    Danielle S. W. Benoit

  5. Department of Biomedical Genetics and Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA

    Danielle S. W. Benoit

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Correspondence to Danielle S. W. Benoit.

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Conflict of Interest

Danielle Benoit and Clyde Overby report grants from National Science Foundation, National Institutes of Health, and New York State Stem Cell Science during the conduct of the study. Benoit and Maureen Newman have a patent (“Compositions Controlled Localized Delivery of Bone Forming Therapeutic Agents.” #9,949,950.Ð’d) licensed to Taithera, and a patent (‘Anti-Fouling Semi-Random Zwitterionic Peptides.’ #2-20003) pending.

Dr. Newman reports grants from National Science Foundation during the conduct of the study and is an employee of Surrozen. Yuchen Wang is employed at Emergent Biosolutions. Dominic Malcolm is a current employee at Athersys, Inc.

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This article is part of the Topical Collection on Regenerative Biology and Medicine in Osteoporosis

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Malcolm, D.W., Wang, Y., Overby, C. et al. Delivery of RNAi-Based Therapeutics for Bone Regeneration. Curr Osteoporos Rep 18, 312–324 (2020). https://doi.org/10.1007/s11914-020-00587-2

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