Strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes.

Jun Wang, Guang Chen, Nan Liu, Xiaoxia Han, Feng Zhao, Lei Zhang, P Chen

Journal: Advances in colloid and interface science 2022;302():102638

PMID: 35299136

Full Text on Elsevier Science View on PubMed

Abstract

In the past decades, the striking development of cationic polypeptides and cell-penetrating peptides (CPPs) tailored for small interfering RNA (siRNA) delivery has been fuelled by the conception of nuclear acid therapy and precision medicine. Owing to their amino acid compositions, inherent secondary structures as well as diverse geometrical shapes, peptides or peptide-containing polymers exhibit good biodegradability, high flexibility, and bio-functional diversity as nonviral siRNA vectors. Also, a variety of noncovalent nanocomplexes could be built via self-assembling and electrostatic interactions between cationic peptides and siRNAs. Although the peptide/siRNA nanocomplex-based RNAi therapies, STP705 and MIR-19, are under clinical trials, a guideline addressing the current bottlenecks of peptide/siRNA nanocomplex delivery is in high demand for future research and development. In this review, we present strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes in the treatment of genetic disorders. Through thorough analysis of those RNAi formulations using different delivery strategies, we seek to shed light on the rationale of peptide design and modification in constructing robust siRNA delivery systems, including targeted and co-delivery systems. Based on this, we provide a timely and comprehensive understanding of how to engineer biocompatible and efficient peptide-based siRNA vectors.

Address: Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.; Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada; Key Laboratory of Chemical Additives for China National Light Industry, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China. Electronic address: [email protected].; Advanced Materials Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250014, China.; Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada; Advanced Materials Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250014, China. Electronic address: [email protected].

DOI: 10.1016/j.cis.2022.102638

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MeSH Terms: Cations, Peptides, RNA Interference, RNA, Small Interfering, Static Electricity