Gene Therapy Today and Tomorrow

Lundström, Kenneth

doi:10.3390/diseases7020037

Cited by 4 publications

(1 citation statement)

References 81 publications

(92 reference statements)

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“…However, uncontrolled gene expression, immune responses to the constituent components of viral particles, and some viral genomes’ relatively small packaging capacities restrict the feasibility of constructs based on recombinant viruses [ 39 , 40 ]. Compared to viruses, the application of non-viral gene therapy approaches using plasmid vectors do not provoke systemic reactions in the organism, and plasmids could be easily manufactured in preparative amounts [ 41 ]. Additionally, the development of new delivery systems has made it possible to achieve high efficiency of transfection both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors

Gatina

Garanina

Zhuravleva

et al. 2021

IJMS

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Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses’ furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases.

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Section: Introductionmentioning

confidence: 99%