Department of Biomedical Engineering, University of Rochester, 308 Robert B. Goergen Hall, Rochester, NY, 14627, USA.
Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
Curr Osteoporos Rep. 2020 Jun;18(3):312-324. doi: 10.1007/s11914-020-00587-2.
The clinical significance, target pathways, recent successes, and challenges that preclude translation of RNAi bone regenerative approaches are overviewed.
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.
本文综述了 RNA 干扰（RNAi）在骨再生中的临床意义、作用途径、最新进展和阻碍其转化的挑战。
RNAi 是一种很有前途的新的骨再生治疗方法，通过刺激或抑制关键信号通路来实现。然而，RNAi 存在着显著的递药挑战。这些挑战包括避免核酸酶降解、实现骨组织靶向和到达细胞质以抑制 mRNA。许多药物传递系统已经克服了稳定性和细胞内定位的挑战，但仍存在蛋白质吸附的问题，导致高达 99%的注射剂量被清除，从而严重限制了药物传递的效果。尽管 RNAi 在骨再生应用中具有许多有前途的特性，但递药挑战仍阻碍其转化。因此，关注药物传递系统的开发对于提高传递效率和骨靶向性至关重要，从而充分发挥 RNAi 的潜力。
