Appraisal for the Potential of Viral and Nonviral Vectors in Gene Therapy: A Review

Abstract

Over the past few decades, gene therapy has gained immense importance in medical research as a promising treatment strategy for diseases such as cancer, AIDS, Alzheimer’s disease, and many genetic disorders. When a gene needs to be delivered to a target cell inside the human body, it has to pass a large number of barriers through the extracellular and intracellular environment. This is why the delivery of naked genes and nucleic acids is highly unfavorable, and gene delivery requires suitable vectors that can carry the gene cargo to the target site and protect it from biological degradation. To date, medical research has come up with two types of gene delivery vectors, which are viral and nonviral vectors. The ability of viruses to protect transgenes from biological degradation and their capability to efficiently cross cellular barriers have allowed gene therapy research to develop new approaches utilizing viruses and their different genomes as vectors for gene delivery. Although viral vectors are very efficient, science has also come up with numerous nonviral systems based on cationic lipids, cationic polymers, and inorganic particles that provide sustainable gene expression without triggering unwanted inflammatory and immune reactions, and that are considered nontoxic. In this review, we discuss in detail the latest data available on all viral and nonviral vectors used in gene delivery. The mechanisms of viral and nonviral vector-based gene delivery are presented, and the advantages and disadvantages of all types of vectors are also given.

Charcot–Marie–Toothneuropathies: Current gene therapy advances and the route toward translation

“…Gene therapy refers to the virally or non‐virally delivered methods aiming to improve a disease phenotype by replacing, adding, silencing, modifying, or repairing genetic material 19 . Each gene therapy method can be administered via numerous routes, and for neurological disorders, the most frequently used are intravenous, intrathecal, intracisternal, intracerebroventricular, intracerebral, and intraneural injections.…”

Breakthroughs in gene therapy: technological progress, current treatments, and future potential

“…The positively charged nature of the polyplex facilitates crossing the cell membrane and integration into the cytoplasm or nucleus. 31,32 They can be natural (e.g., gelatin, cationic cellulose, cationic dextran, etc) or synthetic. One example of a synthetic is polyethylenimine (PEI), which has high transfection efficiency and when linked to a fluorophore provides protection from enzymatic degradation, has shown high transfection efficiency and low cytotoxicity.…”

“…However, this may result in lower transfection efficiency, and modifications can be made to produce peptide dendrimers that have positively charged groups to enhance ability to pass through the cellular membrane. 31,32 A number of inorganic materials have been used to create nanoparticles for delivery of genetic material, including metallic compounds, quantum dots, and carbon nanotubes, among others. 31,32,34 Inorganic materials tend to be more stable, with high biocompatibility and negligible cytotoxicity.…”

“…31,32 A number of inorganic materials have been used to create nanoparticles for delivery of genetic material, including metallic compounds, quantum dots, and carbon nanotubes, among others. 31,32,34 Inorganic materials tend to be more stable, with high biocompatibility and negligible cytotoxicity. Metallic-based nanoparticles, including gold and silver, have especially low toxicity, are easily fabricated and can be modified for more specific targeting.…”

Response Surface Methodology to Efficiently Optimize Intracellular Delivery by Photoporation

“…Instrumental to understanding and harnessing the functioning of biological systems at their most fundamental levels is the intracellular delivery of molecules (e.g., small biomolecules, nucleic acids, proteins and synthetic nanomaterials) that do not passively diffuse across the cell membrane under normal circumstances [ 1 , 2 , 3 ]. To this end, a plethora of intracellular delivery methods has been developed, which can be categorized as either carrier-mediated [ 4 , 5 , 6 , 7 ] or membrane-disruption-mediated methods [ 8 ]. Though carrier-mediated delivery shows great therapeutic potential, particularly for in vivo applications, interest in physical membrane-disruption-mediated delivery techniques has risen over the past few years, especially for in vitro or ex vivo manipulation of cells.…”