China 
Africa 
Explore chapters and articles related to this topic
Enzymes for Prodrug-Activation in Cancer Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
In the gene therapy-based approach GDEPT frequently studied enzyme/prodrug combinations are herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV), cytosine deaminase (CD) of E. coli/5-fluorocytosine (5-FC), cytochrome P450/cyclophosphamide/ifosfamide (CPA/IFA), and nitroreductase/CB1954 (5-(1-aziridinyl)-2,4-dinitrobenzamide, 5-(aziridin-1-yl)-2,4-dinitrobenzamide). Key feature of GDEPT is apart from improved tumor regression via bystander effects the cell-specific delivery of a coding gene cloned into a vector. This has, e.g., been achieved by Pandha et al. (1999) for genetic prodrug activation therapy of breast cancer with the system cytosine deaminase/fluorocytosine by means of a therapeutic cassette that contained the E. coli cytosine deaminase gene driven by the tumor-specific erbB-2 promoter so that drug activation is restricted to cells expressing this oncogene. Erbs et al. (2000) described a cancer gene therapy by AdV-mediated transfer of a bifunctional yeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene.
Gene Therapy in Tissue Engineering: Prospects and Challenges
Published in Rajesh K. Kesharwani, Raj K. Keservani, Anil K. Sharma, Tissue Engineering, 2022
This type of gene therapy involves introduction of a suicide gene into certain target cells that initiate apoptosis in them (Figure 3.12). This technique has been found to be most useful in case of cancer cells and called cancer suicide gene therapy (CSGT). The delivery of the suicide genes involves viral or synthetic vectors, which are guided to the target cancer cells by specific antibodies and ligands. Such vector must have the capability to discriminate between target (cancer) and nontarget (normal) cells. The two major suicide gene therapeutic techniques that are currently followed are: cytosine deaminase/5-fluorocytosine and the herpes simplex virus/ganciclovir.
Advances of engineered extracellular vesicles-based therapeutics strategy
Published in Science and Technology of Advanced Materials, 2022
Hiroaki Komuro, Shakhlo Aminova, Katherine Lauro, Masako Harada
Outside of siRNAs and miRNAs, other common genetic-based drugs used for EV-mediated therapeutic delivery include mRNAs, DNA, gRNA, shRNA, CRISPR/Cas9. Rather than indirectly affecting mRNA expression levels, direct mRNA delivery is straightforward and simple. An example of mRNAs delivery by EVs used as a therapeutic can be seen in Erkan et al [288]. They genetically engineered EVs to carry the mRNA of a suicide gene, cytosine deaminase, fused to an uracil phosphoribosyltransferase (UPRT) and injected it into glioblastoma tumor mice models [288]. They found that the mRNA carrying EVs suppressed tumor growth by 70% compared to the control [288]. These researchers also noted the inhibitory effect of the mRNA suicide gene against schwannoma [289]. Alternatively, mediated delivery of DNA by EVs can be seen in Morishita et al. who loaded biotinylated CpG DNA into EVs [290]. They presented the CpG DNA on the surface by first transfecting B16BL6 cells with a fusion of biotin binding protein streptavidin (SAV) and the EV surface protein lactadherin (LA) [290]. The SAV-LA presenting EVs was isolated and combined with biotinylated CpG DNA, which allowed for the binding to SAV and presentation of the DNA [290]. The mediated delivery of CRISPR/Cas9 can be seen with Kim et al. who through electroporation loaded cancer cell-derived EVs with CRISPR/Cas9 and PARP-1 sgRNA [100]. By turning on apoptotic pathways, the researchers found that these EVs inhibited cancer cell proliferation in vivo and in vitro, and cancer cell-derived EVs had better delivery and accumulation compared to epithelial-derived EVs [100]. Besides miRNA and siRNA, other nucleic acids like DNA and mRNA are also being investigated for their EV-mediated therapeutic potential.