User:Kulkarni2022/sandbox

Whereas, apoptosis causes degradation of cellular components without eliciting an inflammatory response.

Suicide gene therapy involves delivery of a gene which codes for a cytotoxic product into tumor cells. This can be achieve by two approaches, indirect gene therapy and direct gene therapy. Indirect gene therapy employs enzyme-activated prodrug, in which the enzyme converts the prodrug to a toxic substance and the gene coding for this enzyme is delivered to the tumor cells. For example, a commonly studied strategy based on transfection of herpes simplex virus thymidine kinase (HSV-TK) along with administration of ganciclovir (GSV), in which HSK-TK assists in converting GCV to a toxic compound that inhibits DNA synthesis and causes cell death. Whereas, direct gene therapy employs a toxin gene or a gene which has the ability to correct mutated proapoptotic genes, which can in turn induce cell death via apoptosis.  For instance, the most researched immunotoxin for cancer therapy is the diphtheria toxin as it inhibits protein synthesis by inactivating elongation factor 2 (EF-2) which in turn inhibits protein translation. Moreover, proapoptotic gene p53 is identified to be frequently abnormal in human tumors.

Strategies to improve suicide gene therapy

Suicide gene delivery can be broadly classified into three groups which include viral vectors, synthetic vectors and cell-based vectors. The most efficient vehicles for gene delivery are viral vectors. Widely used viruses for gene therapy include retrovirus, adenovirus (Ads), lentivirus and Aden-associated viruses (AAVs). Non-viral vectors like synthetic vectors were used to combat certain disadvantages of viral vectors like immunogenicity, insertional mutagenesis to name a few. Synthetic vectors refer to use of nanoparticles, like gold nanoparticles, to delivery genes to target cells. Lastly, cell-based vectors employ stem cells as carriers of suicide genes. In the last few years, cell-mediated gene therapy for cancer using mesenchymal stem cells (MSCs) was patented.

Bystander effect (BE) in suicide gene therapy

The bystander effect is phenomenon as a result of which it is possible to kill untransfected tumour cells located adjacent to transduced cells in suicide gene therapy. As hundred percent transduction of all tumor cells is very difficult to achieve, BE is critical feature of suicide gene therapy.