The source of this article is Israel21c: http://tinyurl.com/bvwsu
Israel's Rosetta Genomics - cracking the RNA code
By Sharon Kanon May 22, 2005
Rosetta Genomics - Our approach is innovative in that it identifies genes
by computer, and only afterwards verifies their existence in a biological
laboratory.
The historical Rosetta stone was found by French soldiers near the town
of Rosetta in northern Egypt, in 1799. It was a basalt tablet inscribed in
196 BCE with a decree of Ptolemy V of Egypt in two languages (Egyptian and
Greek), using three scripts (hieroglyphic, demotic, and Greek). French
scholar Jean-Francois Champollion used it to derive a key for translating
Egyptian hieroglyphics.
Since that time, Rosetta has been used as a term for the ability to crack
previously indecipherable codes.
The name truly suits the Israeli biotech startup Rosetta Genomics, which
has developed a new discipline: discovering microRNA, which until recently,
was considered an unimportant part of DNA. Just like the historic
hieroglyphics from which the company drew its name, everyone saw it, but
for a long time, no one could decipher it.
Rosetta Genomics kicked off Israel's 57th Independence Day celebrations a
day early with a reception and conference called 'Leading the MicroRNA
Revolution' last week. Held at the Weizmann Institute of Science in
Rehovot, the conference brought together scientists and investors
interested in learning about the developments and discoveries of the
company which until recently, had been kept confidential.
The young, Rehovot-based company has good reason to celebrate. Rosetta has
now discovered and identified more micro RNAs (gene regulators) than any
other research center in the world. The company has identified specific
microRNAs associated with prostate cancer and lung cancer (currently
engaged in pre-clinical animal studies), Epstein Bar Virus, HIV, and Herpes
Simplex Virus.
"From the start, our goal was to achieve a scientific breakthrough that
would lead to the development of products for diagnosis and treatment of
disease in humans," said Dr. Isaac Bentwich, founder and CEO of Rosetta.
Most genomic research has been concerned with proteins, and the genes that
encode proteins and turn them into cells of a certain type. The DNA region
that encodes these proteins, however, constitutes only 2% of DNA. Up until
two years ago, the other 98% of the genome was considered to serve no
function. It was even known as 'junk DNA'.
"For 40 years, research has focused on protein encoding DNA, because it was
assumed that all the rest was just there, serving no purpose," said
Bentwich. "We focused our attention on a field that was rather neglected.
The basic idea was to look for a new group of genes that did not encode
proteins. The amazing thing is that we found them."
Bentwich calls what followed "a scientific earthquake."
"All of a sudden, it turned out that what were thought to be useless genes
were of decisive importance. They are far from being junk DNA. A series of
discoveries proved that extensive regions of junk DNA (that do not encode
proteins) are produced by the cell, and preserved throughout its evolution.
This is evidence that they have a function."
Rosetta Genomics has found a way of using advanced computer technology to
reveal the encoding genes through the microRNA genes. This is now one of
the hottest topics in biology. Published research in the field shows that
these genes are linked to, and affect, a variety of diseases, such as
diabetes, cancer, anemia, and neurological disorders.
Rosetta Genomics' great innovation is that it has managed to find a large
number of genes that couldn't be identified through known technological
means, Bentwich says.
The breakthrough has attracted a slew of high profile Israeli investors:
Pharmaceutical gian Teva, Leon Recanati and his investment company Glenrock
Israel; VCON Telecommunications CEO and former Scitex CEO Yair Shamir; Agis
Industries president and chairman Moshe Arkin; Israeli high tech pioneer
Uzia Galil; and Prof. Michael Sela, Israel Prize laureate and former
president of the Weizmann Institute of Science.
Bentwich first got his idea to focus on the role of microRNAs while
studying meditation in the Himalayas in 1999.
"I've spent long periods in India," he says, "I studied Tibetan Buddhism
and various meditation techniques related to tantra. The inspiration came
at the end of four months of studying meditation in the Himalayas, not far
from the city of Dharamsala. The idea was linked to a puzzle that has
preoccupied me since I was 15 years old. I'm referring to the basic puzzle
of biology how every cell in the body has the same DNA, yet different cells
are differentiated into various types: muscle cells, nerve cells, brain
cells, etc. Science still doesn't know the full answer to the central
question of what causes cells to function differently," he told Globes.
He established Rosetta in 2000, with the support of his father, Prof. Zvi
Bentwich, an immunologist, and one of the world's leading AIDS researchers.
Isaac Bentwich returned to Israel, told his father about his idea, and
started to promote it. His father joined the effort, and is currently both
chief scientist of the company and chairman of its scientific advisory board.
Speaking at last week's conference, the elder Bentwich proudly gave a brief
summary of the scientific discoveries that have marked Rosetta's journey.
"We have discovered 180 microRNAs, and hundreds are in the pipeline.
Rosetta is in a position to own 80% of all the known microRNAs," he said.
"The company began looking for microRNAs several years before other
scientists believed they existed. It gave us an edge," the younger Bentwich
added.
According to him, Rosetta's other edge in the field is its computer system.
"Up until now, the conventional approach was biological, based on the
removal of RNA from the cell. Our approach is innovative in that it
identifies genes by computer, and only afterwards verifies their existence
in a biological laboratory. The success is primarily thanks to Rosetta's
teamwork. We are blessed with an amazing group of talented, creative,
dedicated young people, computer people and biologists, who have succeeded
in tackling the huge technical challenges we faced."
"The computer finds these genes by analyzing the genomic formats. That's
what's 'exotic' about our story. Only after finding them in a dry run do we
look for biological verification to confirm the discovery."
"Rosetta Genomics has combined scientific disciplines in an original way.
The combination of biotechnology and bioinformatics with genetics is
innovative and revolutionary. So is the idea of trying use a computer to
predict genes, and proving the prediction in a laboratory only afterwards.
In the second stage, we're trying to take segments of genes, and link them
with diseases. After verification, we can try to devise treatment for the
diseases from those segments."
According to Bentwich, the first stage that of gene prediction and
verification has been achieved. There are already patents and several dozen
genes have already been proven. The company is now linking genes to diseases.
"These treatments will be based on microRNA, which scientists until
recently thought were junk genes. It is now clear to everyone that they are
goldmines. Rosetta Genomics has reached the applications stage. In this
stage, we'll conduct animal trials on genetic splices. We are collaborating
with medical companies, and Rosetta Genomics' know-how will be the basis
for the medical treatments of the next two decades."
Zvi Bentwich jut returned from a conference in Boston at the beginning of
May, and he reported on a rising interest in the field, noting an
exponential explosion of articles published on microRNAs since 2001. In the
year 2002, Time magazine wrote that microRNAs was one of the ten most
important discoveries of the year.
"One scientist [at the conference in Boston] who had said that there were
probably only about 255 microRNAs, now admitted that he was wrong. He put
the number on the blackboard, and crossed it out. Now the scientific
community has accepted the fact that there are a large number of
microRNAs," he said.
After keeping their operation secret for a number of years, Rosetta is
beginning to make noise with its discoveries. An article on Rosetta?s chip
platform has been accepted by the prestigious journal Genome Research, and
will be published soon
Showing the relationship between the DNA, RNA, and protein on a slide, the
senior Bentwich commented: "MicroRNAs are a small part of the RNA. They
connect with the messenger (mRNA) to create protein. All microRNAs come
into the world to regulate the process of creating proteins."
"Picking out microRNAs was like finding a needle in a haystack.
Bioinformatics was the basis of Rosetta when it was first established. The
company also developed a proprietary system to detect and identify microRNA
signals (they light up) on a chip, and also a biological system to locate
microRNAs in a sequence."
"What can we do with it? When we see that there are 18 times more microRNAs
in a diseased tissue as compared to a normal tissue, which can happen in
cancer, we have the possibility of intervening."
A recent press release was distributed to participants at the conference
last week: Rosetta Genomics scientists found that if they silence one
microRNA in a cluster in an EBV infected cell, there is a dramatic
reduction in the infection of human cells by EBV.
Prof Bentwich stated: "This is the first proof that viral encoded microRNAs
are important for viral replication and has immediate relevance to
development of antiviral drugs."
Keynote speaker at the conference was Technion Professor Aaron Ciechanover,
co-winner of the Nobel Prize in Chemistry in 2004, and Chairman of the
Scientific Advisory Board of Rosetta, a position he took before he won the
Nobel Prize.
"When I first heard about the company, I was a skeptic; then, I became a
believer; and now I am very enthusiastic," said Ciechanover. "When it
started off as a small software company in Jerusalem, I said you won't get
any place without a wet lab. Now the company is well organized - with a
strong bioinformatics branch; and labs that validate their identifications."
Among the guests at the conference was Uzia Galil, a pioneer in industry in
Israel. Galil, most of whose investments are in consumer electronics told
ISRAEL21c that Rosetta is the only biotechnology company in which he is
investing. "It is the most promising."
Dr. Joshua Rosensweig, Chairman of the First International Bank of Israel
(and now a member of the Rosetta Genomics Board), commented that when the
company first came to him for financial advice, he gave advice and then
asked: "How can I invest?"
"We have had a burst of business activity," said Sharon Kaspi, VP Business
Development. "The company is currently in the midst of negotiations for
several important contracts for commercialization and collaboration."
Weizmann Institute of Science Department of Molecular Genetics director
Prof. Doron Lancet, one of the heads of Israel's genome project, had the
final word.
"Rosetta Genomics is working in the hot new field of genome research. It is
utilizing scientific discoveries that have changed the previous paradigm.
That's a revolution."
(Based on a report in Globes)
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