Plasmids employed do not generally replicate in mammalian cells. Non-viral gene delivery systems normally involve the transfer genes carried on plasmid DNA. Gene delivery systems can be grouped into non-biological (chemical and physical approaches of introducing plasmid DNA to mammalian cells) or biological (viruses and bacteria). Thus, DNA is normally combined with a gene delivery vehicle of some type, commonly known as a vector, to protect and mediate effective tissue or cell entry of the gene of interest. 4, 5 Furthermore, a vehicle for effecting tissue or cell entry is also required, due to the poor efficiency of spontaneous DNA uptake. Since naked DNA is rapidly cleared or degraded in vivo by phagocytic immune cells or extracellular nucleases, a means of protecting the transgene is required. Independent of the therapeutic strategy chosen for delivery, the target cells can include the tumor cells themselves, immune cells or tissue such as muscle to act as a source of protein production.Įfficient delivery of the therapeutic gene to the target tissue or cell is the most significant hurdle for successful gene therapy. Another expansion of the concept is cell therapy, where the therapeutic gene is not expressed by the tumor cell but instead produced within the target tissue from newly introduced vectors pre-transfected with genes (discussed below). Therapeutic molecules delivered are not confined to pieces of DNA, and can be RNA (e.g., to inhibit expression of a disease causing gene), or indeed the delivery agent itself may be engineered to be cytotoxic to the cancer cell (oncolytic therapy). The process generally involves introduction of DNA to a cell (transfection), which encodes for a protein and the necessary genetic elements required for expression of the gene of interest to effect successful protein production. Therapeutic agents utilized in gene therapy strategies are typically encoded by DNA and produced within target cells, such as cancer cells. 3 The basic principle lies in the delivery of a nucleic acid effecting the expression of a gene of interest (transgene) in the desired location of the patient's body. Gene therapy has evolved from conceptually focusing on the treatment of monogenetic disorders such as cystic fibrosis, severe combined immunodeficiency (SCID) and muscular dystrophy, to a broader potential including approaches to produce therapeutics in vivo or inducing cell death, and is being investigated and indeed employed clinically for a wider range of both inherited and acquired diseases. Gene therapy is a realistic prospect for the treatment of all cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. 2 For patients with such metastatic cancers, the development of alternative therapies is essential. Conventional therapies for cancer such as chemotherapy and radiotherapy are characterized by poor survival rates due to multiple factors including tumor development of drug-resistance and their lack of tumor specificity, resulting in undesirable side effects on healthy cells and therefore limitations on therapeutic dose. 1 Many patients, by the time of presentation, have already developed secondary tumors (metastases), which are generally responsible for fatalities. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.Ĭancer is the most common cause of death in developed countries. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally.
An emerging family of vectors involves bacteria of various genera. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment.
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