MVGTs are bacteria that have been modified to include genetic material for transfer into human cells. The purpose of the gene transfer is to influence the activity of the human cells, for example adding a missing function in a person with a genetic condition, adding a new function not typical of that cell type, or causing tumor cells to stop growing or die. The process of transferring genetic material from bacteria to mammalian cells is called “bactofection.”
The FDA guidance relates to the production of MVGT drug products to be administered to patients in clinical trials. This process begins with a bacterial culture from which a single colony is selected and grown. The gene of interest is inserted into that bacteria, usually in the form of a small circular DNA molecule called a plasmid; growing the bacteria therefore expands the number of copies of the engineered plasmid. These modified bacteria are then processed for administration to patients. The processing of the MVGT sometimes includes killing or weakening the bacteria to limit its ability to cause a serious infection. When the bacteria are introduced into the body, they target a specific site and are killed (lysed), releasing the gene of interest into the human cells where it can perform its intended function.
Aside from MVGT, there are other methods of gene delivery, including viral vectors and chemical gene transfer. Viral vectors are very efficient at transferring DNA to human cells, but they carry risks of inflammation and toxicity to target and non-target tissues. Chemical gene transfer methods avoid the infection risks of viral or bacterial vectors, though they are much less efficient at transferring DNA to target cells. MVGT products are less efficient than viral vectors, and like viral vectors, they have the potential to cause infections or immune responses (this risk is a clear focus of the current guidance). Despite these drawbacks, MVGT products have significant advantages over alternative viral vectors and chemical gene transfer methods, the most prominent being the simplicity of the technique and the ability to target specific cells or tissues in the body.
One of the most promising applications of MVGTs is in fighting cancer. The ability of MVGTs such as Salmonella to travel specifically to tumors has made it possible to target cancer tumor cells without harming other non-tumor cells. The approaches to fighting tumor growth with MVGTs currently include activating genes that increase the host’s immune response against tumor cells, and cutting off blood flow to the tumor. Genetically modified MVGTs can also be used to help doctors find tumors by using radio-tracer genes that can be seen in positron emission tomography (PET) scans. MVGTs are being tested in clinical trials in humans, however there are currently no FDA approved treatments using MVGTs or other gene therapy methods.
See webpages by National Institutes of Health, The American Medical Association and the Mayo Clinic for general information about gene therapy.