EMBL granted Geneva Biotech an exclusive license for synthetic baculoviral genomes created by EMBL researcher Imre Berger. Baculoviruses are commonly used to produce proteins but their genomes are unstable at large scale, reducing protein yields. Berger developed "SynBac" genomes that removed unstable regions to create viruses that maintain high protein expression levels even after multiple amplifications for large-scale production. The new technology licensed by Geneva Biotech has the potential to transform large-scale production of biologics for pharmaceutical applications.

1. 6/25/2016 EMBL grants exclusive license for synthetic baculoviral genomes to Geneva Biotech | ComplexINC
http://complexinc.eu/news­centre/details/article/embl­grants­exclusive­license­for­synthetic­baculoviral­genomes­to­geneva­biotech/ 1/2
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The baculovirus genome as it occurs in nature
is unstable in scale‐up. New SynBac genomes
from EMBL overcome this handicap.
EMBL grants exclusive license for synthetic baculoviral genomes
to Geneva Biotech
January 27, 2015
EMBL Enterprise Management Technology Transfer GmbH
(EMBLEM), the exclusive partner of the European Molecular
Biology Laboratory (EMBL) for technology transfer, has granted
Geneva Biotech an exclusive license for exploitation of
intellectual property covering novel minimal baculoviral
genomes.These synthetic viral nanosystems (SVNs) were created
in the laboratory of ComplexINC coordinator Imre Berger at
EMBL, harnessing advanced synthetic biology techniques.
Baculovirus is a highly efficient delivery system for recombinant
genes into eukaryotic cells, with great impact on the production
of eukaryotic protein, including high‐value targets for
pharmaceutical development, notably GPCRs, ion channels and
their complexes. This method is also suitable for producing
vaccines against influenza, herpes, cervical cancer and others.
More recently, baculovirus has emerged as a versatile tool for
gene therapy.
However, baculoviruses are plagued by a handicap which can be
severely detrimental notably for the production of important
biologics such as multicomponent vaccines, at pharma‐relevant scales. Scaling up baculovirus expression is in fact
accompanied by accumulation of viruses carrying mutations and deletions, most pronouncedly in the recombinant
DNA expression cassettes inserted into the virus. This results often in markedly reduced recombinant protein
yields.
“To produce biologics at large scale, you need fermenters processing large volumes of cell culture, which in turn
requires large volumes of high‐titer baculovirus for infection” explains Daniel Fitzgerald, CEO of Geneva Biotech.
“To obtain large volumes of your virus, you need to amplify several times. Each time you amplify, you
accumulate damaged virus which is no longer able to produce your target. It really is a no‐win situation.”
The Berger laboratory has developed earlier MultiBac™, the lead technology for multiprotein production by a
baculovirus, which is already successfully commercialized by Geneva Biotech.
“We encountered this problem with baculoviruses containing large recombinant DNA inserts already some time
ago.” remembers Imre Berger. “In the relatively small scale required for structural biology applications, where
today only a few milligrams are required, we could circumvent the scale‐up problem by reducing the number of
amplification steps and working with low titers.”
This obviously is not an option for pharma‐scale applications, and a solution to the scale‐up problem has
remained elusive.This challenge has now been addressed. Comparative genome analysis and intense data mining
was applied to identify regions of the baculovirus genome that were potentially harmful and required

2. 6/25/2016 EMBL grants exclusive license for synthetic baculoviral genomes to Geneva Biotech | ComplexINC
http://complexinc.eu/news­centre/details/article/embl­grants­exclusive­license­for­synthetic­baculoviral­genomes­to­geneva­biotech/ 2/2
reengineering. Professional bioinformatics support was provided by the IStLS (Information Services to
LifeSciences). “We removed these regions, and also the DNAs that had no apparent use in lab culture. Next, we
designed in silico optimized viral genomes that we could rewire to our purposes.” explains Berger who lead the
work at EMBL. Efficient synthetic DNA technologies were then used to create the new genomes in vitro. “ The
ComplexINC project is ideal for carrying out this work, with all the protein and bioprocessing know‐how present
in this consortium.” says Berger. EMBL’s technology transfer EMBLEM immediateley recognized the value of the
novel, synthetic minimal baculovirus genomes and filed a patent application based on this invention.
The proprietary technology, SynBac™, is now offered by Geneva Biotech. “We already received numerous requests
from leading pharma companies.” concludes Daniel Fitzgerald. “Our technology has the potential to transform
pharma‐scale baculoviral production of next‐generation biologics, for the treatment of disease.”
Geneva Biotech offers a portfolio of intelligent protein production platform technologies and exploits synthetic
biology approaches for a wide variety of applications including the development of novel molecular therapeutic
tools and small molecule modulators of natural and synthetic signaling pathways that are at the heart of human
disease.
EMBL is Europe’s flagship laboratory for the life sciences – an intergovernmental organisation with more than 80
independent research groups covering the spectrum of molecular biology. It operates across five sites:
Heidelberg, Hamburg, Grenoble, Monterotondo and EMBL‐EBI Hinxton.
EMBLEM currently manages a portfolio of more than two hundred and fifty patents/copyrights and over our
hundred license contracts. EMBLEM’s technology portfolio spans the Life Sciences in the broadest sense and
includes enabling technologies, molecular tools & techniques, instruments & devices as well as software
programmes & databases. IStLS supports public research institutes, service providers and enterprises in the realms
of bioinformatics, biotechnology, biochemistry, biology and health sciences in the processing, presentation and
management of information. IStLS offers consultancies, practice‐oriented seminar and training courses, long‐
term coaching, research services and surveys. Particular areas of activity include functional genomics,
proteomics, and microarray technologies.
Your Contact:
Hannah Weber (Eurice), Imre Berger (EMBL Grenoble) and Daniel Fitzgerald (Geneva Biotech)
Links:
Geneva Biotech
EMBL Enterprise Management Technology Transfer GmbH (EMBLEM)
ComplexINC’s MultiBac platform technology
Information Services to Life Sciences IStLS
EMBL multiexpression tools
SynBac article
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