Applied DNA Sciences, Inc. has begun initial Research and Development pilots for the manufacture of DNA for use in DNA-based therapeutics for two companies. Several other companies have requested proposals for additional DNA-based therapeutics.
In one project, the company is engaged in evaluation of a DNA therapeutic with a U.S.-based customer and in the second, the company is conducting an evaluation of two animal vaccines with Evvivax srl, an Italian biotech company focused on healthcare for companion animals. These pilots will be developed using the company’s proprietary and patented large-scale PCR (polymerase chain reaction) DNA production processes and devices.
“PCR-production of DNA offers advantages over ‘plasmid produced’ DNA,” Dr. James Hayward, president and CEO of Applied DNA, said. “The goal of this pilot is to quantify those advantages for use in our animal vaccines.”
The new pilots complement current agreements to supply PCR-produced DNA to suppliers of diagnostics, according to Applied DNA. The company’s current customers develop the diagnostic tests, while Applied DNA acts as the long-term supplier of their customized DNA.
It is a natural extension to the company’s roadmap of DNA-tagging commercial pharmaceutics to secure supply chains of approved drugs, the company continued in a statement. The DNA tags are short, have no biological function by design, and are present as traceable “excipients,” which aid in the manufacture of finished drugs, but are not the Active Pharmaceutic Ingredients (APIs). The company’s portfolio now will include (longer) functional DNA therapeutics.
DNA vaccines have until now, been based primarily upon “plasmid” delivery. Plasmids are small, circular, double-stranded molecules of DNA found in bacteria and yeast. These molecules have traditionally been the tools used to manufacture DNA.
However, a plasmid-based technology for gene therapy suffers from a number of drawbacks that include: a) the active DNA only represents about 30-50 percent of the plasmid, b) the remaining 50-70 percent of the plasmid contains multiple genetic components unrelated to the DNA vaccine that may have unintended consequences in humans, c) the plasmid-containing bacteria must be grown in very large vessels, over many days, to yield DNA supplies adequate for vaccines, d) the bacteria used to produce the plasmids contain toxins and pyrogens, that can cause illness and fevers if present in the DNA preparation that is given to a patient.
PCR-produced DNA is very pure, especially compared to plasmids. Bacteria are not used during manufacturing. The reaction starting materials are limited to the nucleotides (adenine, thymine, guanine and cytosine) contained within the target sequence, an enzyme called polymerase, the template for the target DNA and primers.
Almost all the starting materials are consumed during the reaction. Any residual reactants are easily removed during purification of the target DNA, due especially to the latter’s far greater size. Most importantly, the PCR-produced DNA contains only the DNA elements required for DNA therapeutic function and is free of any of the extraneous genetic elements intrinsic to a plasmid-based carrier.
Filed Under: Drug Discovery
