Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology

Yuhua Weng; Qianqian Huang; Chunhui Li; Yongfeng Yang; Xiaoxia Wang; Jie Yu; Yuanyu Huang; Xing-Jie Liang

doi:10.1016/j.omtn.2019.12.004

Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology

Mol Ther Nucleic Acids. 2020 Mar 6:19:581-601. doi: 10.1016/j.omtn.2019.12.004. Epub 2019 Dec 17.

Authors

Yuhua Weng¹, Qianqian Huang², Chunhui Li¹, Yongfeng Yang³, Xiaoxia Wang⁴, Jie Yu³, Yuanyu Huang⁵, Xing-Jie Liang⁶

Affiliations

¹ Advanced Research Institute of Multidisciplinary Science, School of Life Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, P.R. China.
² Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
³ Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, P.R. China.
⁴ Institute of Molecular Medicine, Peking University, Beijing 100871, P.R. China.
⁵ Advanced Research Institute of Multidisciplinary Science, School of Life Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, P.R. China. Electronic address: yyhuang@bit.edu.cn.
⁶ Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, P.R. China. Electronic address: liangxj@nanoctr.cn.

Abstract

Due to a series of systemic and intracellular obstacles in nucleic acid (NA) therapy, including fast degradation in blood, renal clearance, poor cellular uptake, and inefficient endosomal escape, NAs may need delivery methods to transport to the cell nucleus or cytosol to be effective. Advanced nanoscale biotechnology-associated strategies, such as controlling the particle size, charge, drug loading, response to environmental signals, or other physical/chemical properties of delivery carriers, have provided great help for the in vivo and in vitro delivery of NA therapeutics. In this review, we introduce the characteristics of different NA modalities and illustrate how advanced nanoscale biotechnology assists NA therapy. The specific features and challenges of various nanocarriers in clinical and preclinical studies are summarized and discussed. With the help of advanced nanoscale biotechnology, some of the major barriers to the development of NA therapy will eventually be overcome in the near future.

Keywords: ASO; CRISPR/Cas; RNAi; drug delivery; gene editing; nucleic acid therapy.

Publication types

Review