Dominic W Malcolm1,2, Yuchen Wang1,2, Clyde Overby1,2, Maureen Newman1,2, Danielle S W Benoit3,4,5,6,7. 1. Department of Biomedical Engineering, University of Rochester, 308 Robert B. Goergen Hall, Rochester, NY, 14627, USA. 2. Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA. 3. Department of Biomedical Engineering, University of Rochester, 308 Robert B. Goergen Hall, Rochester, NY, 14627, USA. Benoit@bme.rochester.edu. 4. Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA. Benoit@bme.rochester.edu. 5. Materials Science Program, University of Rochester, Rochester, NY, USA. Benoit@bme.rochester.edu. 6. Department of Chemical Engineering, University of Rochester, Rochester, NY, USA. Benoit@bme.rochester.edu. 7. Department of Biomedical Genetics and Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA. Benoit@bme.rochester.edu.
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. 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.
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. 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.
Entities:
Keywords:
Bone regeneration; Drug delivery systems; RNAi; miRNA; siRNA