Applications and developments of gene therapy drug delivery systems for genetic diseases

Abstract

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Keywords: Gene therapy drugs; Genetic diseases; Nano-delivery system; Non-viral vectors; Viral vectors.

Graphical abstract

Fig. 1

Schematic illustrations of the siRNA-encapsulating prism and release mechanism. Reprinted with permission from . Copyright 2016 American Chemical Society.

Fig. 2

General overview and timing. (A) sgRNA design. (B) Vector construction. (C) Microinjection and genotyping. Reprinted with permission from . Copyright 2019 Elsevier.

Fig. 3

Systemic gene editing results in widespread dystrophin expression. Reprinted with permission from . Copyright 2017 Springer Nature.

Fig. 4

Schematic diagram of gene editing of integrated lentiviral vector. Reprinted with permission from . Copyright 2018 Elsevier.

Fig. 5

(A) Synthetic route employed for lipidoids synthesis. (B) Intracellular delivery of Cas9:sgRNA RNP complex loaded LNPs for gene editing. (C) Chemical structures of amine head (R) groups. Reprinted with permission from . Copyright 2018 Royal Society of Chemistry.

Fig. 6

Schematic diagram of gene editing of MMP-9shRNA. Reprinted with permission from . Copyright 2017 Elsevier.

Fig. 7

Preparation process of NP/pZNF580/RBCs and their gene delivery by crossing extracellular and intracellular barriers. Reprinted with permission from ref . Copyright 2018Royal Society of Chemistry.

Fig. 8

Schematic diagram of CRISPR/Cas9-mediated DMD deletions. Reprinted with permission from ref . Copyright 2016Elsevier.