80 DRUG DISCOVERY
Perfecting a viral pack mule
iruses aren’t always bad. In fact, scientists can harness the capabilities of some viruses for good – modifying the viruses to carry drug molecules, for example.
V
One useful virus has been cowpea mosaic virus (CPMV), a plant pathogen that can be modified to aid in tumour detection and even chemotherapy. In a new study, researchers at The
Scripps Research Institute (TSRI) in California report that, based on its structure, a hollowed-out version of CPMV could also be effective in human therapies. “By studying the structure of the viral
particles, we can get important information for transforming this plant virus into a useful therapeutic,” states TSRI associate professor Vijay Reddy, senior author of the study. TSRI researchers have studied CPMV
for decades. In fact, the structure of the virus was first determined in the lab of TSRI professor Jack Johnson, who also served as a co-author on the new study. CPMV is an especially useful drug
delivery agent because it has about 300 different sites on its external and internal surfaces where researchers can attach
molecules. Because CPMV is a plant virus, it is harmless to humans. To eliminate any lingering concerns of viral genomes entering the human body, scientists have created ‘empty’ versions of CPMV, called eVLPs (empty virus-like particles), which lack the virus’s genetic material.
high-resolution image of the 3D structure of CPMV eVLPs. The image showed the structures of
eVLP particles are very similar to CPMV particles, giving scientists the go-ahead to use the same modification strategies on both. This finding was in sync with a previous study showing eVLPs at a lower resolution. The current study also revealed a
“The eVLP is no longer a virus; it is just a
protein capsule,” explains Reddy. The question has been whether eVLPs
of CPMV retain the same structure in the absence of viral genome as natural CPMV viral particles. In the new study, Reddy and his colleagues used an imaging technique called x-ray crystallography to create a
new detail on both eVLPs and CPMV virus particles. Mass-spectrometry-based proteomics analysis identified multiple proteolytic cleavage sites – a spot where amino acids are cut off – on one of the proteins on the particle surface. Previous research had indicated only one such cleavage site in this region, not three. With the new information, researchers know not to add crucial molecules to those amino acids in case they get clipped off too. Reddy says the new study opens the
door to future research on using eVLPs to carry drug molecules and designing customised vaccines.
For more information visit
www.scripps.edu
Adenoviruses launched to aid drug discovery A
MSBIO has launched a comprehensive collection of pre-packaged human full-length cDNA ORF and miRNA adenoviruses. Featuring more than 1,240 pre-
packaged human miRNA precursor adenoviruses and 30,000 pre- packaged human full-length cDNA ORF adenoviruses the collection sets out to enhance high-throughput drug discovery, improve functional genomic studies, and make life science research more efficient. Recombinant adenoviruses are
extremely efficient gene delivery systems that are widely used in human gene therapy and in vitro gene functional studies. Compared to other transfection methods or viral delivery systems, recombinant
www.scientistlive.com
gene expression can often be observed in less than 24 hours. Using the recombinant
adenovirus, a high gene expression level can be achieved in a wide range of hosts including both dividing and non-dividing mammalian cells. The collection will particularly benefit researchers who work with difficult- to-transfect primary cells and stem cells, as well as those who use full- length cDNA clones. AMSBIO guarantees the
adenovirus offer unmatched transduction efficiency. Traditionally, adenoviral vector cloning
and virus production has typically required four to six weeks to complete. With AMSBIO pre-packaged recombinant adenovirus,
expression of its pre-packaged recombinant adenovirus products.
All pre-packaged adenovirus have been validated by western blot in HEK293 cells.
For more information visit
www.amsbio.com
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