NEW YORK—In April, the Mount Sinai School of Medicine, located here granted licensing rights for U.S. Patent, No. 6,855,523 to Hamilton Thorne Biosciences, putting the Beverly, Mass.-based DNA technology and automated instrumentation company in a strong position to market a potential competitor to PCR: linear and exponential rolling circle amplification (RCA).
"PCR testing is considered the gold standard for nucleic acid testing, and it meets the needs for high-volume, high-throughput organizations like universities, pharmaceutical companies and others," says Dr. Harry G. McCoy, Hamilton Thorne's president. "But PCR is also a bit too cumbersome and complex to reach the full market that we think molecular diagnostics could—and should—reach.
"We think that simplified techniques like RCA are ideal to get testing closer to the patient, at places like hospitals, clinics and smaller reference laboratories."
First described in 1995, RCA uses processes similar to those employed by viruses to replicate their genomes in a host cell. In the first phase of the RCA process, a quasi-circular DNA probe containing two strand displacement primers and two ligation primers is allowed to anneal with the target molecule. After circularization of the probe and insertion of the DNA polymerase, primers and oligonucleotides, the polymerase attached to the first strand-displacement primer and begin to copy the circular probe. After a complete revolution, the copied strand is displaced by the same polymerase, which continues to replicate this circular template. So, with just one extension primer, RCA effectively provides linear amplification.
If a second strand displacement primer is encoded in the circular probe, the process grows exponentially in a process called ramification amplifying method (RAM).
"In the simplest terms, you have a single DNA circle with a primer on it," explains Dr. David J. Lane, Hamilton Thorne's vice president of research and development. "You throw in one of a variety of different enzymes, the primer extends around the circle, and when it meets the tail, it keeps on going for a fairly explosive DNA synthesis."
The technology isn't new, McCoy says, and this Mt. Sinai patent is one of a line of patents stretching back to the original filing based on the work of Dr. David Zhang, an associate professor of pathology at Mt. Sinai. Dr. Zhang also is the inventor of two of Hamilton Thorne's patented core technologies: RAM, and the hybridization signal amplification method.
"Together with previously issued patents in the area of rolling circle amplification, we believe [this latest patent] will represent a valuable asset to our licensee, Hamilton Thorne Biosciences, as it increases its development and commercialization activities in a number of diagnostic areas," said Dr. W. Patrick McGrath, executive director of Mt. Sinai Medical School's Office of Industrial Liaison.
The issuing of the license is also a statement of the faith that Mr. Sinai and Dr. Zhang have in Hamilton Thorne.