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I. Introduction<\/strong> Gene therapy is an evolving approach for treatment of diseases bestowed upon by genetic abnormalities.\u00a0It works by delivery of a suitable recombinant nucleic acid<\/span> which in turn helps in regulation and repair, addition and deletion of genes for therapeutic regime. Millions of people are effected by cancer every year and failure of conventional therapies including chemotherapy, radiotherapy etc. necessitates to look for alternative treatment modalities. In this regard gene therapy is viewed as an alternative to conventional medical therapies for the treatment of several diseases, including cancer.<\/p>\n Out of the different approaches of gene therapy, suicide gene therapy has been able to make a special mention in clinical trials. In suicide gene therapy, genes of interest are inserted into tumor cells via vectors and in presence of a suitable prodrug the cancer cells destroys itself when the delivered gene converts the prodrug into a toxic drug and its metabolites<\/span>. This type of gene therapy have targeted various types of carcinomas including lung, liver, skin, cervix, gastrointestinal<\/span> and lymphomas.<\/p>\n Suicide gene therapy comprises of different types of systems. The widely applied systems are herpes<\/span> simplex virus thymidine kinase gene (HSV<\/span>-TK) with prodrug ganciclovir (GCV), cytosine<\/span> deaminase uracil<\/span> phosphoribosyltransferase\u00a0(CD-UPRT) with prodrug 5-FC<\/span>, carboxyl esterase\/irinotecan (CE\/CPT-11), varicella zoster virus thymidine kinase\/6-methoxypurine arabinonucleoside VZV-tk (ara-AMP<\/span> to araATP), XGPRT (6TX to 6TXnMP), nitroreductase Nfsb\/5-(aziridin -1-yl)-2, 4-dinitrobenzamide (NTR\/CB1954), cytochrome p450-ifosfamide and liver p450 (cyclophosphoamide to degraded toxic product).<\/p>\n A successful gene therapy module should consist of the following elements, a gene which encodes for a therapeutic moiety, a plasmid-based expression system which directs the \u00a0functioning of a gene inside the target cells, and a delivery vector helps in the delivery of the gene to its target location. Gene expression plasmids are equipped with the therapeutic gene as well as the components to control the transcription<\/span>, translation, expression and stability of the final product in host cells.<\/p>\n One of the important aspects where we can bring about the versatility of a gene therapy regime is design of the delivery vector. A delivery system must ensure the protection of the loaded therapeutic gene from degradation in intracellular<\/span> or extracellular environments. Further it should also ascertain the delivery into the specific cells. There are various types of gene delivery vehicles including viral vectors<\/span> which although are very much efficient but are less preferred due to its highly immunogenic nature.<\/p>\n Over the years efforts have been streamlined towards designing non-viral vectors<\/span> that would be able to achieve efficient gene expression and specificity as demonstrated by viral vectors<\/span> along with the ability to bypass the host immune system. Approaches such as electroporation<\/span>,sonoporation<\/span>,magnetofection, ballistic DNA<\/span> injection etc. are also being studied for gene transfer, but have not been very much successful in clinical applications, primarily because of their invasive nature. Recently several \u00a0polymer-based systems, lipopolyplex based systems, polyamine systems, micelle based systems, nanoparticles<\/span>, quantum<\/span> dots etc. are currently under investigation for gene delivery applications.<\/p>\n In case of lipofection, a cationic liposome<\/span> composed of cationic lipid\u00a0N<\/em>[1-(2,3-dioleyloxy)propyl]-N,N,N<\/em>-trimethylammonium chloride) (DOTMA) and the colipid dioleoylphosphatidylethanolamine (DOPE) in 1:1 ratio is used for formation of the gene carries. Other commonly used cationic lipids include 3\u03b2-(N,N<\/em>-dimethylaminoethane) carbamoyl] cholesterol,dioctamido-decylamidoglycylspermine,1,2-dimyristyloxypropyl-3 dimethylhydroxyethyl ammonium bromide, 1,2-bis(oleoyloxy)-3 (trimethylammonio)propane, 2,3-dioleyloxy-N<\/em>-[2-(sperminecarboxamido)ethyl]-N,N<\/em>-dimethyl-1-propanaminium trifluoroacetate. For site-specific gene delivery, targeting ligands can be covalently linked to the vectors to ascertain delivery to target tissues. However, the stability and biocompatibility of these systems should be taken into account when it comes to in vivo<\/span> applications. The biocompatibility of the inorganic vectors can be improved through PEGylation<\/span> and efforts have been made to develop non-viral vectors<\/span> with minimal toxicity through chemical modifications.<\/p>\n Molecular imaging guided gene therapy plays an important role towards development of a successful gene delivery vector and ascertaining its subsequent fate. Fluorescent based specific probes or contrast agents allows the tracking of a intracellular<\/span> gene delivery vector and also monitor the gene expression. Organic dyes that have been a choice for these applications suffer from several drawbacks such as photobleaching, poor water solubility, less stability , toxicity etc. Semiconductor quantum<\/span> dots (QDs) have been also considered for bioimaging and labelling applications due to their size,composition dependent tunable emission. But in this case too, since most of the quantum<\/span> dots comprises of heavy metal, their toxicity is a concern. Also, QDs have been reported to exhibit undesirable photo blinking, as well as solubility issues in biological applications.<\/p>\n Recently, few atom metal nanoclusters have emerged as new class of candidates for bioimaging as a result of their excellent fluorescence properties, high photostability, bio friendly nature. Metal nanoclusters of silver, gold and copper have been demonstrated as imaging agents in both\u00a0in vitro<\/em>\u00a0and\u00a0in vivo<\/span><\/em>\u00a0systems with minimal toxicity. Also, several polymers like chitosan, DNA<\/span>, protein,\u00a0 PAMAM (polyamidoamine), etc. as well as small molecules like peptides, ligands, amino acids etc have been successfully applied as a template or stabilizer\u00a0 in the synthesis of these metal nanoclusters. Hence, these metal nanoclusters incorporated into a suitable gene delivery vehicle which is loaded with a therapeutic suicide gene can allow efficient tracking of gene delivery and monitor subsequent \u00a0gene expression for cancer therapy.<\/p>\n Guest contribution of Deepanjalee Dutta. This cornerstone article is based on the paper and her scientific work,\u00a0Cationic BSA Templated Au\u2013Ag Bimetallic Nanoclusters As a Theranostic<\/span> Gene Delivery Vector for HeLa Cancer Cells.\u00a0<\/span><\/em><\/strong><\/p>\n Morgan,\u00a0R.\u00a0A. Live and Let Die: A New Suicide Gene Therapy Moves to the Clinic\u00a0Mol. Ther.<\/em>\u00a02012<\/strong>,\u00a020,\u00a011\u201313\u00a0DOI: 10.1038\/mt.2011.273<\/p>\n Han, S.; Mahato, R. I.; Sung, Y. K.; Kim, S. W. Development of Biomaterials for Gene Therapy. Molecular Therapy<\/em> 2000<\/strong>, 2<\/em> (4), 302\u2013317.<\/p>\n Shao, D.; Li, J.; Pan, Y.; Zhang, X.; Zheng, X.; Wang, Z.; Zhang, M.; Zhang, H.; Chen, L. Noninvasive Theranostic<\/span> Imaging of HSV<\/span>-TK\/GCV Suicide Gene Therapy in Liver Cancer by Folate-Targeted Quantum Dot-Based Liposomes. Biomater. Sci.<\/em> 2015<\/strong>, 3<\/em> (6), 833\u2013841.<\/p>\n Vankayala, R., Kuo, C.-L., Nuthalapati, K., Chiang, C.-S. and Hwang, K. C., Nucleus-Targeting Gold Nanoclusters for Simultaneous In Vivo Fluorescence Imaging, Gene Delivery, and NIR-Light Activated Photodynamic Therapy. Adv. Funct. Mater.,<\/em> 2015<\/strong>, 25: 5934\u20135945. doi:10.1002\/adfm.201502650.<\/p>\n Dutta, D.; Chattopadhyay, A.; Ghosh, S. S. Cationic BSA Templated Au\u2013Ag Bimetallic Nanoclusters As a Theranostic<\/span> Gene Delivery Vector for HeLa Cancer Cells. ACS Biomater. Sci. Eng.<\/em> 2016<\/strong>, 2<\/em> (11), 2090\u20132098.<\/p>\n Related Products<\/strong><\/p>\n GenElute Kit (Sigma)<\/a><\/p>\n EtBr (Himedia)<\/a><\/p>\n
\n\u2022 Gene therapy as an alternative treatment to conventional medical therapies
\n\u2022 Suicide gene therapy as a potential approach
\nII. Suicide Gene Therapy Systems<\/strong>
\n\u2022 Different types of suicide gene therapy systems
\n\u2022 Examples of widely applied systems
\nIII. Elements of a Successful Gene Therapy Module<\/strong>
\nIV. Gene Delivery Vectors<\/strong>
\nV. Lipofection and Site-Specific Gene Delivery<\/strong>
\n\u2022 Use of cationic liposomes for gene delivery
\n\u2022 Targeting ligands for site-specific gene delivery
\n\u2022 Importance of biocompatibility and stability in in vivo applications
\nVI. Molecular Imaging Guided Gene Therapy<\/strong>
\nVII. Conclusion<\/strong>
\n\u2022 Future prospects of gene therapy and its potential in clinical applications.<\/p>\n
\nReferences<\/h3>\n