Current Landscape and Emerging Opportunities of Gene Therapy with Non-viral Episomal Vectors

Abstract

Gene therapy has proven to be extremely beneficial in the management of a wide range of genetic disorders for which there are currently no or few effective treatments. Gene transfer vectors are very significant in the field of gene therapy. It is possible to attach a non-viral attachment vector to the donor cell chromosome instead of integrating it, eliminating the negative consequences of both viral and integrated vectors. It is a safe and optimal express vector for gene therapy because it does not cause any adverse effects. However, the modest cloning rate, low expression, and low clone number make it unsuitable for use in gene therapy. Since the first generation of non-viral attachment episomal vectors was constructed, various steps have been taken to regulate their expression and stability, such as truncating the MAR element, lowering the amount of CpG motifs, choosing appropriate promoters and utilizing regulatory elements. This increases the transfection effectiveness of the non-viral attachment vector while also causing it to express at a high level and maintain a high level of stability. A vector is a genetic construct commonly employed in gene therapy to treat various systemic disorders. This article examines the progress made in the development of various optimization tactics for non-viral attachment vectors and the future applications of these vectors in gene therapy.

Circular Single-Stranded DNA: Discovery, Biological Effects, and Applications

“…Compared with plasmids, the use of a CssDNA vector has several advantages. First, in order to ensure safety and high-efficiency expression in host cells, plasmids must eliminate the unnecessary bacterial backbone sequences, which consists of elements necessary for the production in bacterial cells, such as antibiotic-resistance genes, and retain their active supercoiled conformation. , In contrast, CssDNA is generated without bacterial backbone sequences through the helper plasmid system and exists solely in a single topological structure. , Second, plasmid DNA can be recognized by the innate immune system causing gene silencing or elimination due to the presence of unmethylated CpG motifs, , whereas CssDNA may not be easily silenced and cleared with low immunogenicity. , Third, in combination with cationic lipids, the smaller size of CssDNA can facilitate nuclear translocation to enhance effects such as achieving a higher level of gene expression . Finally, CssDNA outperforms plasmid templates for gene writing because of its single-stranded feature. ,, …”

“…309,310 In contrast, CssDNA is generated without bacterial backbone sequences through the helper plasmid system and exists solely in a single topological structure. 15,129 Second, plasmid DNA can be recognized by the innate immune system causing gene silencing or elimination due to the presence of unmethylated CpG motifs, 311,312 whereas CssDNA may not be easily silenced and cleared with low immunogenicity. 15,252 Third, in combination with cationic lipids, the smaller size of CssDNA can facilitate nuclear translocation to enhance effects such as achieving a higher level of gene expression.…”

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“…At the same time, the detection of blood concentration showed that 111In-IMP-288 could be rapidly absorbed into bone marrow without blood toxicity, which indicates that the combination of TF12 and 111In-IMP-288 May be applied to prostate treatment in the future [45][46][47][48][49]. In addition, the combination of TF12 and 111In-IMP-288 for treating metastatic colorectal cancer has entered the clinical phase I/II study.…”

Trop2: A Key Player in Oncology - From Research to Clinical Application

“…At the same time, the detection of blood concentration showed that 111In-IMP-288 could be rapidly absorbed into bone marrow without blood toxicity, which indicates that the combination of TF12 and 111In-IMP-288 May be applied to prostate treatment in the future [45][46][47][48][49]. In addition, the combination of TF12 and 111In-IMP-288 for treating metastatic colorectal cancer has entered the clinical phase I/II study.…”