Which activator is more active?
The mini-ring DNA is 14 times more effective at delivery and much more successful at destroying breast cancer in mice than the plasmid vector.
Healthy cells of the human body secrete nanoscale bubbles (exosomes and microvesicles) that transfer genetic material to other cells. These extracellular vesicles can become transporters carrying drugs and activating their genes into cancer cells to destroy them.
A study conducted by Masamitsu Canada and his colleagues from Michigan State University and Stanford University on mouse models of breast cancer is devoted to the development of an effective and safe method of delivering genes to cancer cells that encode enzymes capable of converting inactive drugs into agents toxic to the tumor. This mechanism underlies gene-directed therapy with the enzyme-prodrug complex.
Prodrugs are intact until they undergo changes in the body. After activation by special enzymes, they are able to fight various conditions, from headaches to cancer. Aspirin is an example of a common prodrug.
The researchers used extracellular vesicles (EV) to deliver genes responsible for the synthesis of thymidine kinase (TK) and nitroreductase (NTR) enzymes to cancer cells. The TK-NTR complex activates the prodrugs ganciclovir and CB1954 in mouse breast cancer cells.
A mini-ring DNA and a regular plasmid – two different gene vectors that are DNA delivery vehicles – were placed in vesicles to choose from them a more convenient option for transportation.
The researchers found that the mini-ring DNA was 14 times more effective at delivery and more successful at destroying breast cancer in mice: TK-NTR expression in cancer cells was significantly higher and prolonged, and about half of the cancer cells died. For effective therapy, at least 1% of tumor cells must be infected with vesicles with TK-NTR genes. Delivery of plasmids, on the contrary, did not lead to the death of tumor cells.
According to the authors, the new approach may in the future become an alternative to chemotherapy for cancer treatment. Standard chemotherapy is not able to distinguish tumor cells from normal tissue, so it kills everything. This non-specificity causes serious side effects and insufficient concentration of the drug in the tumor.
With the help of vesicles with mini-ring DNA, treatment can be targeted, and due to compatibility with the human body, this type of delivery is accompanied by a minimal risk of undesirable immune reactions that are characteristic of other types of gene therapy.
If EVs prove to be equally effective in humans, they will be an ideal platform for gene delivery. The first clinical trial conducted by another group of scientists is due to begin in the United States in the near future, and it will use EV and RNA molecules to treat metastatic pancreatic cancer.
While this study is being prepared for launch, Canada and his team are continuing to study and test EVs, working to improve their effectiveness and safety, bringing them closer to being used as a gene therapy to fight cancer in humans.
Article by M. Kanada et al. Microvesicle-mediated delivery of minicircle DNA results in effective gene-directed enzyme prodrug cancer therapy published in the journal Molecular Cancer Therapeutics.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to MSU Today: Tiny bubbles in our body could fight cancer better than chemo.