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DNAtrix is focussed on curing cancer.  DNAtrix’s first product candidate, Delta-24-RGD, represents a potential breakthrough product that could be applied for the treatment of both local and regional malignant tumors. The novel DNAtrix technology, Delta-24-RGD, has several advantages for treating cancer.  Animal data suggest that Delta-24-RGD can enhance both radiation- and chemo-therapy.  The company’s goal is to fast-track this potential breakthrough therapy through the drug development process in the United States.

Adenoviruses such as Delta-24-RGD replicate by hijacking the cellular machinery used to control cell division. The virus attacks human cells that harbor the adenovirus receptor – usually the mucosal cells of the upper respiratory system. Once inside the cell, the virus produces a protein that knocks out the Rb/p16 pathway, causing the cell to begin to divide. The virus then forces the cell to produce viral proteins and viral DNA in large amounts. At a certain point, the cell is so full of new viral particles that it bursts, releasing virus into the surrounding tissue where it can go on to infect other cells.

Although it may take a couple of days, a healthy immune system can successfully fight off adenovirus. In fact, most of us have been infected with adenovirus over the course of our lives, with no long-term health consequences except for cold-like symptoms.

The delta24-RGD adenovirus, by contrast, is a conditionally-replicating adenovirus that has been engineered to infect cancer cells effectively. The “delta24” in the name means that 24 base pairs of DNA have been deleted (so called delta-24 or ∆24) from the wild-type adenovirus genome. The result is that the virus can no longer hijack the machinery used to control cell division. For the virus to reproduce, the cell must already be dividing, either naturally or as a result of a disruption of the Rb/p16 pathway associated with a cancer cell.

In a cancer cell, the “delta24” virus can replicate efficiently, resulting in the death of the cancer cell and release of progeny virus, which can then infect neighboring cancer cells. This “chain reaction” has been shown to be effective for treating cancer in animal models of disease.

Another unique feature of the DNAtrix approach is the addition of “RGD-4C”, a seven amino acid peptide that has been inserted into the surface of the virus in the fiber protein.

Typically, adenovirus infects mucosal tissues because they express high levels of the adenovirus receptor protein. Several different studies have shown that cancer cells generally express these adenovirus receptor proteins at low levels. The result is that the infection of cancer cells by adenovirus is inefficient. To solve this problem, DNAtrix’s virus has been engineered to infect cells via highly expressed proteins called the integrins, which are abundant on most cancer cells. The “RGD peptide” expressed on the surface of the engineered virus allows the delta24-RGD virus to easily infect most cancer cells.

Taken together, the delta24 and RGD modifications to the adenovirus maximize the ability of the virus to destroy malignant cells while minimizing the side effects on healthy cells.

As shown in the figure above, the virus can be injected directly into a tumor. The virus replicates inside tumor cells until the cells begin to burst (cell lysis). Once a cell bursts, the newly released virus travels to other, nearby cancer cells to repeat the infection cycle. This chain reaction of cell killing is expected to be particularly effective in treating malignant brain tumors, where it is often difficult to define the boundary between tumor and healthy tissues during surgery to remove the tumor.