Biomaterial-based gene therapy

Abstract

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial-based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial-based gene delivery systems. Furthermore, the current applications of biomaterial-based gene therapy are summarized.

Keywords: biomaterial; gene therapy; nonviral vector; viral vector.

FIGURE 1

Overview of biomaterial‐based delivery systems for gene therapy.

FIGURE 2

A review of biomaterial‐based gene therapy. Exogenous nucleic acid entering the human body combined with different types of viral vectors, nonviral vectors, and physical methods. The Exogenous nucleic acid illustration is part of a figure reproduced with permission from Ref. , Copyright 2022 © Elsevier B.V. The different types of viral vectors, nonviral vectors, and physical methods is reproduced with permission from Ref. , Copyright 2022 © Elsevier B.V. The application in patients with different diseases is created with BioRender.com.

FIGURE 3

Schematic diagram of the physical methods of exogenous gene therapy. (A) PS laser setup and optical light pathway for irradiation. Reproduced with permission from Ref. , Copyright 2021 © Wiley‐VCH GmbH. (B) Hydroporator: hydrodynamic cell deformation‐induced intracellular delivery of nanomaterials. (i) the design and operation principles. (ii) The delivery mechanism (iii) layout of hydroporator (iv) High‐speed microscope images. (v) FITC‐dextran in K562 cells using hydroporator. Reproduced with permission from Ref. , Copyright 2019 © Royal Society of Chemistry. (C) Principle of magnetofection. Reproduced with permission from Ref. , Copyright 2011 © Elsevier B.V.

FIGURE 4

(A) Mesoporous silica nanoparticles (MSNs). (B) Structures of AuNPs. (C) Schematic illustration of the magselectofection procedure. Reproduced with permission from Ref. , Copyright 2011 © Elsevier B.V.

FIGURE 5

(A) Biogenesis scheme of three kinds of extracellular vesicles (microvesicles, exosomes, and exosome apoptotic bodies) and constituents. (B) Schematic diagram of the exosome‐based chondrocyte‐targeted miRNA delivery system for the targeted delivery of miR‐140 to treat osteoarthritis. Reproduced with permission from Ref. , Copyright 2020 © American Chemical Society.

FIGURE 6

(A) Schematic representation of MN‐mediated gene and drug delivery in the treatment of skin cancer. Reproduced with permission from Ref. , Copyright 2021 © Elsevier B.V. (B) Schematic diagram of the nanoparticle‐encapsulated MN system in 3D gels. Reproduced with permission from Ref. , Copyright 2021 © Elsevier B.V. (C) SEM of PLGA microparticles with RG752, RG502, and RG502H. Reproduced with permission from Ref. , Copyright 2006 © Elsevier B.V. (D) Microsphere‐based multicompartment system for nucleic acid delivery. Reproduced with permission from Ref. , Copyright 2017 © Wiley Periodicals, Inc.

FIGURE 7

(A) DNA hydrogel‐based delivery system for small‐molecule drugs. Reproduced with permission from Ref. , Copyright 2021 © Springer Nature Limited. (B) Schematic diagram of monolayer and multilayer scaffolds. Reproduced with permission from Ref. , Copyright 2022 © Elsevier B.V. (C) Visualization of PEI‐pIL‐1Ra nanoparticles in a collagen‐hydroxyapatite scaffold. (i) SEM image of the porous microarchitecture in CHA scaffolds. (ii) SEM image of a CHA scaffold activated with PEI‐pIL‐1Ra nanoparticles. Reproduced with permission from Ref. , Copyright 2020 © Lackington, Gomez‐Sierra, González‐Vázquez, O'Brien, Stoddart and Thompson.

FIGURE 8

(A) Physical and functional retention of LNP‐RNA vaccine. Reproduced with permission from Ref. , Copyright 2022 © The Authors. Published by Elsevier B.V. (B) Structures of lipid nanoparticle nucleic acid vectors. Reproduced with permission from Ref. , Copyright 2021 © The Authors. Published by American Chemical Society. (C) The mRNA is encapsulated in lipid nanoparticles. Reproduced with permission from Ref. , Copyright 2021 © Elsevier Ltd. (D) mRNA engineering process used as a SARS‐CoV‐2 vaccine. Reproduced with permission from Ref. , Copyright 2020 © Wiley‐VCH GmbH.