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.

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

“…Gene-based therapy is considered one of the most revolutionary technology approaches for various biomedical applications that has advanced along with DNA recombination technology and gene cloning technology [1]. Unlike targeted or conventional drug therapy, gene-based therapy acts at the DNA or mRNA level to intentionally modulate gene expression in specific cells for preventive or therapeutic actions through correcting gene transcription and translation processes [1], affording long-lasting and curative benefits in the treatment of various inherited and acquired diseases [2][3][4].…”

“…Gene-based therapy is considered one of the most revolutionary technology approaches for various biomedical applications that has advanced along with DNA recombination technology and gene cloning technology [1]. Unlike targeted or conventional drug therapy, gene-based therapy acts at the DNA or mRNA level to intentionally modulate gene expression in specific cells for preventive or therapeutic actions through correcting gene transcription and translation processes [1], affording long-lasting and curative benefits in the treatment of various inherited and acquired diseases [2][3][4]. Considering that gene-based therapy implies the introduction of a functional tunable therapeutic gene to directly repair/amend or replace the altered genetic material at the molecular level [5,6], this unique approach may facilitate the modulation of genetic information through the exogenous stimulation of key signaling pathways in targeted cells, attaining various intended functions (e.g., the differentiation of certain cells into specialized cells, the production of cellular therapeutics or the stimulation of the apoptosis process in cancer cells) and offering innovative approaches for improving the targeted functions as well as fostering both the advancement of new therapeutics based on cell gene correction and their clinical translation [4,7].…”

“…Currently, the "library" of gene therapy drugs mainly comprises plasmid DNA (pDNA), small interfering RNA (siRNA), microRNA (miRNA) and short hairpin RNA (shRNA) along with antisense oligonucleotides (ASO) [1,8]. Nonetheless, exploiting the full potential of gene-based therapy in academic or clinical practices entails certain strategies that are able to tackle the main drawbacks faced in gene delivery (e.g., low stability and serum protein interactions, recognition by immunologically active factors, reduced targeting and cell uptake abilities, low endosomal escape and reduced transfection activity) [1,2,9].…”

“…Currently, the "library" of gene therapy drugs mainly comprises plasmid DNA (pDNA), small interfering RNA (siRNA), microRNA (miRNA) and short hairpin RNA (shRNA) along with antisense oligonucleotides (ASO) [1,8]. Nonetheless, exploiting the full potential of gene-based therapy in academic or clinical practices entails certain strategies that are able to tackle the main drawbacks faced in gene delivery (e.g., low stability and serum protein interactions, recognition by immunologically active factors, reduced targeting and cell uptake abilities, low endosomal escape and reduced transfection activity) [1,2,9]. Therefore, the selection of an appropriate gene delivery carrier that is capable of specifically targeting selected cells, avoiding the stimulation of the innate immune system or toxicities and proficiently passing through complex intracellular barriers to safely reach the nucleus, protecting the incorporated gene from extracellular or intracellular enzymes and consequently advancing therapeutic efficacy represents one of the most critical aspects in gene therapy drug delivery [10,11].…”

Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2

“…Chemical and biochemical processes such as calcium phosphate co-precipitation, and viral carrier delivery systems have been tested successfully. In this case, some of the preferred choices include retroviruses, adenoviruses, and lentiviral vectors [12]. However, some of these methods have shown drawbacks in high cytotoxicity and immunogenicity and low delivery yields for the transported bioactive molecules [13].…”