Potential Applications for Targeted Gene Therapy to Protect Against Anthracycline Cardiotoxicity

Abstract: In recent times, several approaches for targeted gene therapy (GT) had been studied. However, the emergence of extracellular vesicles (EVs) as a shuttle carrying genetic information between cells has gained a lot of interest in scientific communities. Owing to their higher capabilities in dealing with short sequences of nucleic acid (mRNA, miRNA), proteins, recombinant proteins, exosomes, the most popular form of EVs are viewed as reliable biological therapeutic conveyers. They have natural access through every biological membrane and can be employed for site-specific and efficient drug delivery without eliciting any immune responses hence, qualifying as an ideal delivery vehicle. Also, there are many research studies conducted in the last few decades on using exosome-mediated gene therapy into developing an effective therapy with the concept of a higher degree of precision in gene isolation, purification and delivery mechanism loading, delivery and targeting protocols. This review discusses several facets that contribute towards developing an efficient therapeutic regime for gene therapy, highlighting limitations and drawbacks associated with current GT and suggested therapeutic regimes.

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Regulation of gene transfection by cell size, shape and elongation on micropatterned surfaces

Journal of Materials Chemistry B ◽

10.1039/d1tb00815c ◽

2021 ◽

Author(s):

Yongtao Wang ◽

Yingjun Yang ◽

Toru Yoshitomi ◽

Naoki Kawazoe ◽

Yingnan Yang ◽

...

Keyword(s):

Gene Therapy ◽

Cell Size ◽

Tissue Repair ◽

Gene Transfection ◽

P Gene ◽

Gene Carriers ◽

Potential Applications

Gene transfection has been widely studied due to its potential applications in tissue repair and gene therapy. Many studies have focused on designing gene carriers and developing novel transfection techniques....

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Optimizing Polyplexes into Synthetic Viruses for Tumor-Targeted Gene Therapy

Non-viral Gene Therapy ◽

10.1007/4-431-27879-6_19 ◽

2006 ◽

pp. 237-245

Author(s):

Ernst Wagner ◽

Julia Kloeckner ◽

Manfred Ogris

Keyword(s):

Gene Therapy ◽

Targeted Gene Therapy

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Thymidine kinase-mediated killing of rat brain tumors

Journal of Neurosurgery ◽

10.3171/jns.1993.79.5.0729 ◽

1993 ◽

Vol 79 (5) ◽

pp. 729-735 ◽

Cited By ~ 101

Author(s):

David Barba ◽

Joseph Hardin ◽

Jasodhara Ray ◽

Fred H. Gage

Keyword(s):

Gene Therapy ◽

Brain Tumors ◽

Tumor Cells ◽

Wild Type ◽

Cns Disorders ◽

Content Type ◽

Potential Applications ◽

Ganciclovir Treatment ◽

The Brain ◽

Fine Print

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.

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