Wednesday June 19, 2013
Most virus tests look for telltale DNA sequences or other markers that signal the presence of a particular pathogen. However, Dr. Adrian di Biscelia's laboratory at the St. Louis University School of Medicine has developed a new open-ended approach that can signal the presence of any virus or other blood-borne pathogen. The technique not only identifies known viruses, but also finds whether there are previously uncharacterized pathogens.
The technique relies on whole-genome next generation DNA sequencing. Whole-genome sequencing refers to reading all the A, T, C, G nucleotides present in the total DNA of a person. With major advances in high throughput sequencing technology over the past several years, the cost and speed of whole genome sequencing has dropped precipitously--to the point that is now practical for individual patients to have their personal genomes sequenced in a matter of hours. The first human genome sequencing took 13 years to finish and was just completed in 2003.
With the complete human genome sequence available as a reference, identifying foreign DNA in human samples is really more of an information processing exercise than a biochemical analysis. Essentially, DNA extracted from a person's blood, for example, can be sequenced and then compared with a reference human genome sequence. If there are extra leftover DNA pieces after this comparison, they must be from some non-human organism in the blood.
If the additional DNA is from a known virus, it is easy to identify it. However, if the extra DNA does not match any known viruses, then it is something new. Comparison of the DNA with known viruses would likely provide valuable information, in most cases, to help classify even new viruses and provide clues as to their virulence. The technique could provide a new way to rapidly catch new emerging viruses, such as the Middle East Coronavirus (MERS) which surfaced about a year ago.
You can read more about this development in St Louis University's press release.
Thursday June 13, 2013
In a unanimous decision the Supreme Court ruled today that natural genes are not patentable. The ruling boils down to the observation that patents must cover new inventions, not simply discoveries of natural phenomena. As stated in the Court's opinion, "genes and the information they encode are not patent eligible...simply because they have been isolated from the surrounding genetic material."
The opinion, written by Clarence Thomas points out that, "The Patent Act permits patents to be issued to '[w]hoever invents or discovers any new and useful . . . composition of matter,'" but, "groundbreaking, innovative, or even brilliant discovery does not by itself satisfy" this criteria. "Myriad did not create or alter either the genetic information encoded in the BCRA1 and BCRA2 genes or the genetic structure of the DNA"
The Court did validate patent claims to synthetic versions of genes containing just the key parts that produce the protein--in other words cDNA (complementary or cloned DNA). With cDNA, fragments of a gene's DNA are pieced together with other pieces of DNA to produce an non-natural construction of a gene. The justices affirmed patent rights to cDNA based on the reasoning that, "the lab technician unquestionably creates something new when cDNA is made." However, it is not clear from the ruling how broad cDNA claims could be. Can a company claim rights to any cDNA made to mimic a particular gene, or are its right limited to the particular cDNA made in their labs?
The Court also specifically pointed out that it has not ruled on genes in which the natural DNA sequence has been altered, innovative methods to isolate genes, and applications that utilize particular knowledge about natural gene sequences. These are all reasonable subjects for patents.
The ruling was not unexpected and will not likely have an immediate effect on the biotech industry or Myriad Genetics as discussed in more detail a related article The Significance of the Myriad Gene Patent Decision. In fact, Myriad's press release emphasized the point that the Court upheld their claims to the synthetic cDNA version of the genes they constructed for their BRCA gene tests. However, the ruling does certainly clear the way for other laboratories to test for the presence of the BRCA gene mutations, especially if they use techniques such as DNA sequencing that do not require synthetic cDNA constructions as references.
While there may be some concern that the ruling may make companies and investors less likely to put resources into new genetic discoveries, it remains to be see if there will be any long term impact on biotech investment and innovation. In fact, the case does clear up some longstanding murkiness about what aspects of genetic discoveries can actually be patented and owned by company. It seems likely that this increased clarity may enable some companies to more confidently invest in research projects without having to worry about unknown patent holders claiming rights to the genes they are working on.
You can find more background about the Myriad case in The Supreme Court Reviews Myriad's Gene Patents, and, for information about gene patents in general, check out Can a Company Really Own Your DNA?
Friday June 7, 2013
Two days ago the Food and Drug Commissioner Margaret Hamburg authorized emergency use of the CDC's Novel Coronavirus 2012 Real-time RT-PCR Assay for the detection of the Middle East Coronavirus (MERS). Under the Pandemic and All-Hazards Preparedness Act which was enacted in 2006 reauthorized in March this year the FDA can allow limited use of a non-approved medical products to address public health emergencies. The FDA authorization grants public health laboratories in the US clearance to use the CDC's MERS detection kit to identify the virus in patient samples.
Last month a similar authorization was granted for a CDC assay to detect the H7N1 Bird Flu. Previous to these two approvals, the last medical devices authorized under the emergency act were for detection of the H1N1 Influenza strain in May of 2009.
On May 29, Health and Human Services Secretary Kathleen Sebelius declared MERS as a potential public health emergency. The authorization of the detection assay for this virus is intended to enable rapid identification and monitoring of the spread of the disease to minimize its potential impact. So far, no cases of MERS have been reported in the US. Worldwide 55 people have been reported to have come down with the virus and 31 of these died. It is the high mortality rate that has caused concern.
MERS is related to the Severe Acute Respiratory Virus (SARS) in that they are both coronaviruses. However, the two viruses are not of the same lineage. According to an announcement from the coronavirus study group, MERS is actually most closely related to bat coronaviruses. However, it does not appear that most of the affected individuals were exposed to the virus by contact with bats. Also, though, there does not appear to be evidence of "sustained community transmission" according to the report. For example, of the 55 cases reported so far, 40 were concentrated in Saudi Arabia. There have only been isolated cases in the other seven countries where it has been reported.
As a result of the limited transmission, the study group believes that the MERS virus strain has jumped from bats to another animal. The thinking is that this other infected animal species is in closer contact with humans than bats, and that it is by interaction with this other viral-carrying animal that most humans become infected. However, the fear, of course, is that the virus might eventually adapt to enable efficient human-to-human transmission allowing it to spread much more rapidly.
You can find more information on MERS at the CDC website, and the About Senior Travel Guide offer a guide for overseas travel.
Friday May 24, 2013
Researchers from the Nabel laboratory at the National Institute of Allergy and Infectious Diseases (NIAID) developed a synthetic nanoparticle flu vaccine that showed much higher effectiveness in both mice and ferrets compared with the standard seasonal vaccine. If the work pans out, it could enable production of a vaccine that provides better protection against more stains of influenza and is easier and faster to produce than the current seasonal vaccines.
The group produced a self-assembling nanoparticle that stimulated a much stronger immune response than the standard flu vaccine by using a fusion of the iron binding protein ferritin to influenza virus protein hemagluttinin (HA). The ferritin protein naturally assembles to form a nanostructure that has 24 protrusions. The ferritin-HA hybrid was designed so that the HA molecules were exposed at the end of the protrusions, enabling the immune system to easily recognize and respond to the antigen. The structure produced an immune response about 10-fold stronger than the standard vaccine in ferrets, which is a common model animal for influenza studies.
Although the antigenic nanoparticle was built using the 1999 strain of H1N1 flu, the ferrets' immune response also protected them against other H1N1 strains with slightly different versions of the HA protein. For more universal flu protection, though, a vaccine would need to contain antigenic nanoparticles displaying HA molecules from other flu strains. There are 17 known HA subtypes.
This work exemplifies general efforts from a number of research groups to develop a more potent and universal vaccine to combat seasonal influenza. The effectiveness of the current seasonal flu vaccines vary significantly from year to year depending on a number of factors, including how well the CDC can guess which strains will likely be in wide circulation for the upcoming season. Also, current vaccines are poorly effective at immunizing the elderly, a segment of the population most at risk for serious health-related complications result from influenza.
Other efforts to improve flu vaccine performance include DNA-based vaccines, research on antibodies that recognize multiple flu strains, and BiondVax's Multimeric-001 which is currently in clinical trials.
You can find more information on the current study at the Nature News.