Mutation Detection is Key to Developing Vaccines

New technologies that detect cell mutations are helping scientists better understand how cells develop resistance to drugs.

Speed matters when it comes to cancer cell mutations. It matters because the faster mutations occur, the more difficult cancer is to treat. That’s why speed is also important in targeting more precise therapeutic treatments.

Life science companies have long used high-throughput sequencing to help develop and commercialize drug therapies. For instance, Connecticut-based 454 Life Sciences, a Roche Holding (OTC Pink:RHHBY) company, uses specific applications to resequence genomes using its GS FLX and GS Junior systems, which can support the sequencing of samples from a wide variety of starting materials, including genomic DNA and bacteria artificial chromosomes.

A new technique may soon be commercialized that could help track the mutations of cancer cells. Scientists at A*STAR’s Genome Institute of Singapore (GIS) have developed a novel technique to precisely monitor and study the evolution of micro-organisms such as viruses and bacteria.

Organisms evolve through mutations. Micro-organisms and viruses and bacteria evolve faster than normal human cells as their rapid lifecycles enable faster selection of advantageous mutations.

Previously scientists had to wait for the selection process to reach maturity to observe mutations and assess their impact.

But an article published in the March issue of Nucleic Acids Research explains that scientists at the GIS have developed a technique that significantly increases the ability of databases to detect mutations, making it possible to catch “evolution in real time.”

That means scientists can now observe the process of mutation as it happens and can catch how organisms or cancer cells develop resistance to drugs.

The new technology, known as LoFreq, combines deep sequencing DNA with computational analysis to detect mutations at extremely low frequencies in as few as one in 1,000 cells.

This approach is currently being used at the GIS to study the dengue virus by characterizing subtle shifts in the viral genome in response to new antiviral drugs.

There are no vaccines yet to treat infection from the dengue virus, which infects more than 100 million people every year and kills as many as 21,000 infected victims.

Colorado-based Inviragen has been conducting second-phase trials of its anti-dengue vaccine in Puerto Rico, Colombia, Singapore and Thailand. The company uses the tools of molecular virology to produce safe viruses or viral proteins that induce protective immune responses. Inviragen is privately held by: Charter Life Sciences, a venture capital firm in Palo Alto, California and Cincinnati, Ohio; Venture Investors of Madison, Wisconsin and Ann Arbor, Michigan; and EDBI and Phillip Private Equity, two Singapore-based investment firms.

In addition to its dengue virus vaccine, Inviragen and its collaborators are looking at novel vaccines to protect against other infectious disease threats, such as hand, foot and mouth disease, Japanese encephalitis and chikungunya, another insect-borne virus that has similar symptoms to dengue.

A company that may have a dengue vaccine on the market as early as 2015 is French pharma Sanofi Pasteur, the vaccine division of Sanofi (NYSE:SNY). Sanofi Pasteur has 14 vaccines in development or submitted for approval, including one for dengue, which is considered a growing threat because it is spreading to new parts of the globe and is already a threat to half of the world’s population. Multiple approaches have been tested to develop a vaccine that covers dengue’s four viral serotypes and can prevent its severe complications, such as hemorrhagic fever. The results of a second-phase clinical trial on adults in the United States demonstrates proof of concept of the lead vaccine candidate.

Sanofi Pasteur is working with the World Health Organization and the Pediatric Dengue Vaccine Initiative, an International Vaccine Institute program funded by the Gates Foundation, to make dengue a vaccine-preventable disease and to accelerate vaccine introduction in pediatric populations where the disease is endemic through disease burden evaluation, vaccine advocacy and vaccine access. Sanofi Pasteur’s dengue vaccine research program includes ongoing clinical studies on both adults and children in endemic regions such as Asia and Latin America.

Dr. Niranjan Nagarajan, one of the principal investigators at the GIS, said using LoFreq to detect viral genome evolution has given researchers the ability to construct better models for transmission of the dengue virus.

“We can also now identify key functional regions in viral genomes by highlighting spots that never mutate or mutate rapidly. In ongoing work, we are developing extensions to LoFreq that can better character mutations in cancer.”

The ability to catch how a cancer cell develops resistance to current drugs may one day be feasible because of the computation analysis that can now be conducted.

This next generation of sequencing datasets is an innovation in computational space, said Ng Huck Hui, executive director at the GIS, in a statement. “We expect that LoFreq will have wide utility in the analysis of viral, bacterial and cancer genome data,” he commented.

 

Securities Disclosure: I, Andrew Topf, hold no direct investment interest in any company mentioned in this article. 

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