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post Posted: May 1 2004, 05:28 PM
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I feel confident your patience will be amply rewarded. They are a relatively low cost operation with significant potential to gain large cash flows. Medium term could see a significant upward valuation given most shares are tightly held. Any big increase in income from pending licensing deals will have an instant effect on thin tradeable percentage of stock.

post Posted: May 1 2004, 01:10 PM
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Second International
‘RNAi-2004-Boston’ Meeting on
“RNA interference: Biology to Drugs & Therapeutics”
Doubletree Guest Suites, Waltham, MA, USA
May 2-4, 2004

maybe add some momentum into the sp action of BLT

post Posted: May 1 2004, 12:49 PM
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Hi adder & jarm

Excellent information - very much appreciated. Please keep up the good work.

Your summary was great, jarm.

I hold BLT for the long term - like many biotechs they are an illiquid stock and its difficult to time an entry point, so I just sit and hold this one



post Posted: May 1 2004, 12:19 PM
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A summary report from the Citigroup bi-annual Medtech & Biotech Bullring re BLT.

Strategy you know.

Competitive advantages bear listing again:

They hold the earliest patents for RNAi in humans and mammals and importantly hold the ONLY issued patents for RNAi in humans and mammals in the UK and US

7 granted, >65 pending (derivative in the main but helpful in creating a firewall) in 19 jurisdictions

Have dedicated partners providing licensed ddRNAi materials

ddRNAi offers unique capability for treatment of a broader range of diseases, including viral diseases and cancers

They have pioneered the field for 10 years and are recognized universally as being the legitimate holders of the IP

Adder has again summarised the technical points but as an aside the technology ought to significantly reduce the time to clinic since the usual preliminary steps involving gene discovery, target identification and validation both in vitro and in vivo, candidate drug screening, lead identification and optimisation are shortened by an anticipated 3 years or more

BLT is involved in in-house therapeutic development programs (mostly HepC and perhaps diabetes) but has strategic collaborations internationally to expand applications (mostly in HIV/AIDS and cancer)

They seek to expend revenue from early licensing to improve self-sufficiency and also sek to establish BLT USA (where they see their future)

Expecting IND filing within a year for ddRNAi therapeutic targets

The Dec 2003 placement supported their expansion plans leaving them with a clear balance sheet

Expect 2004 share options to largely fund costs in the short term


post Posted: Apr 30 2004, 09:06 PM
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RNAi markets set for strong growth

- 30/04/2004 - The market for RNA interference (RNAi) products used as research tools and therapeutics is still at an embryonic stage, but looks set to more than double in value by the end of the decade, according to new market research.

RNA interference (RNAi) – also known as gene silencing - involves the use of double stranded RNA (dsRNA). Once inside the cell, this material is processed into short 21-26 nucleotide RNAs termed siRNAs that are used in a sequence-specific manner to recognise and destroy complementary RNA, effectively switching off the activity of the gene and halting production of the protein for which it codes.
The major use of RNAi reagents is in research but it partially overlaps that of drug discovery and therapeutic development.

Ireland’s Research and Markets, which compiled the report, noted that the markets for RNAi are difficult to define as no RNAi-based product is in clinical development yet. It is estimated to be $300 million (€251m) currently and will increase to $400 million in 2005 and $850 million by the year 2010.

Meanwhile, the value of the drug discovery market based on RNAi can be assessed at $500 million currently with increase to $650 million in 2005 and further doubling to $1 billion in the year 2010. And even if only a handful of products get into the market by the year 2010, this market will expand to $3.5 billion, based on revenues from sales of RNAi-based drugs

The report compares RNAi with other antisense approaches using oligonucleotides, aptamers, ribozymes, peptide nucleic acid and locked nucleic acid.

Various RNAi technologies are described, along with design and methods of manufacture of siRNA reagents. These include chemical synthesis by in vitro transcription and use of plasmid or viral vectors. Other approaches to RNAi include DNA-directed RNAi (ddRNAi) that is used to produce dsRNA inside the cell, which is cleaved into siRNA by the action of Dicer, a specific type of RNAse III. MicroRNAs are derived by processing of short hairpins that can inhibit the mRNAs. Expressed interfering RNA (eiRNA) is used to express dsRNA intracellularly from DNA plasmids.

Delivery of therapeutics to the target tissues is a crucial consideration, and is one of the primary reasons why it has taken so long for antisense-based therapeutics to emerge as a realistic new product class. The report notes that siRNAs can be delivered to cells in culture by electroporation or by transfection using plasmid or viral vectors. Meanwhile, in vivo delivery of siRNAs can be carried out by injection into tissues or blood vessels or use of synthetic and viral vectors, according to R&M.

Because of its ability to silence any gene once the sequence is known, RNAi has been adopted as the research tool to discriminate gene function. After the genome of an organism is sequenced, RNAi can be designed to target every gene in the genome and target for specific phenotypes. Several methods of gene expression analysis are available and there is still need for sensitive methods of detection of gene expression as a baseline and measurement after gene silencing.

To this end. RNAi microarrays have been devised that can be tailored to meet the needs for high throughput screens for identifying appropriate RNAi probes, used to analyse gene function and identify new drug targets. And with the advent of vector-mediated siRNA delivery methods it is now possible to make transgenic animals that can silence gene expression stably, providing powerful models for exploring disease processes.

RNAi can be rationally designed to block the expression of any target gene, and this includes genes for which traditional small molecule inhibitors cannot be found. Areas of therapeutic applications include virus infections, cancer, genetic disorders and neurological diseases.

However, despite the exquisite selectivity of the technology, side effects can result from unintended interaction between an siRNA compound and an unrelated host gene. So if RNAi compounds are designed poorly, there is an increased chance for non-specific interaction with host genes that may cause adverse effects in the host.

post Posted: Apr 22 2004, 10:22 PM
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Research and Markets: RNAi - The Hottest Technology In Biotechnology


post Posted: Apr 10 2004, 11:35 AM
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Southern Cross Equities confident that BLT has recovered from its difficulties in digesting the recent capital raising. Their IP insurance will also stand them in good stead against expected piracy.

post Posted: Apr 1 2004, 11:35 PM
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RNAi offers promise to biotech firms

post Posted: Apr 1 2004, 10:46 AM
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Some more excellent news for the development of the technology behind the BLT IP.

New RNA Libraries Can Selectively Inactivate Human Genes

03/24/04 -- Researchers have produced vast libraries of short segments of ribonucleic acid (RNA) that can be used to turn off individual human and mouse genes to study their function.

The libraries will be made widely available to laboratories studying human biology and disease. The researchers are optimistic that the libraries will become a powerful research tool for gene analysis and discovery.

Two independent research groups reported on their respective RNA interference (RNAi) libraries in the March 25, 2004, issue of the journal Nature. Gregory Hannon of the Cold Spring Harbor Laboratory and Howard Hughes Medical Institute investigator Stephen J. Elledge at Harvard Medical School and Brigham and Women's Hospital led the first group. The joint lead authors were Patrick Paddison, Jose Silva and Douglas Conklin in Hannon's laboratory. René Bernards of The Netherlands Cancer Institute led a second group.

Commenting on the significance of the studies in the journal Nature, Andrew Fraser at the Wellcome Trust Sanger Institute wrote: "As no single laboratory can specialize in every aspect of gene function, the general availability of these [short hairpin RNA] libraries as a communal resource is a major step forward, harnessing the screening expertise of the entire mammalian-cell research community."

RNA interference is a technique used with much success by researchers to switch off genes in lower organisms, including the fruit fly Drosophila and the roundworm C. elegans. Researchers stumbled upon this powerful tool for gene analysis when they discovered that introduced sequences of double-stranded RNA identical to a target messenger RNA actually triggered degradation of the messenger RNA.

Messenger RNA molecules are the genetic templates for proteins. In constructing proteins, the mRNA template is transcribed from DNA genes and transported to the ribosomes -- the cell's protein "factories" that are large complexes of protein and RNA. RNA interference is a technique that essentially shuts down the activity of the gene under study.

"But RNAi didn't work in the vast majority of human or mouse cells because there are additional antiviral responses that recognize double-stranded RNA," said Elledge. "While the machinery to do RNAi is in mammalian cells, the antiviral machinery makes the introduced RNA toxic, and the cells die."

Researchers subsequently discovered that short segments of interfering RNA could be introduced into mammalian cells and remain unnoticed by the antiviral machinery, said Elledge. Furthermore, they discovered that the cell itself could be engineered to make interfering RNAs by introducing the gene for short hairpin RNA molecules that fold back on themselves to create a small RNA.

To construct a library of mammalian genes for short hairpin RNA molecules, Hannon and his colleagues first had to settle on an optimal design for a short-hairpin-RNA molecule. "We tested a lot of different things -- for example, the length of the hairpin, the loop structure, the structure of the transcript and what promoters to use," said Hannon. "And we arrived at an optimal structure for this phase of the science."

Hannon emphasized, however, "that set of parameters is something that is going to evolve continuously. There have been many advances over the last year in understanding of the biochemistry of RNAi. So, we are now constructing even more effective structures and even more effective delivery vehicles which will be built into future generations of this library."

Once an optimized basic design of the short hairpin RNA molecule was finished, the researchers then produced a library of genes for short hairpin RNAs that could target 9,610 human genes and 5,563 mouse genes. The genes chosen were those that were likely to be involved in human disease, or to be key molecular switches in the cell.

The library of genes was integrated into a retroviral vector that was capable of shuttling the genes into other cell types. The researchers also incorporated a DNA "bar-coding" system, by which each RNA molecule can be tagged with a unique DNA sequence.

By determining the sequence of a given bar code for a short hairpin RNA, researchers using the library to screen for genes affecting a specific cellular process can identify which RNA molecule among the thousands in the library is switching off the activity of a particular gene.

But the retroviral vectors used for shuttling the short hairpin RNAs into cells only went so far. They were not efficient for getting genetic short hairpin RNAs into all cell types. That's where an innovative technique developed by Elledge and his colleagues came in handy. This technique, called "mating-assisted genetically integrated cloning" (MAGIC), greatly assisted the transfer of the short hairpin RNA library into all cell types via bacterial mating.

In order to validate that the library worked in human cells, the researchers tested it in a genetic screen designed to report defects in human proteasome function. The proteasome is a key component of the machinery by which the cell breaks down unwanted proteins. "This was a thorough test of the system because there are a great number of different genes whose loss could interfere with proteasome function," said Elledge. "We found quite a few genes, and concluded that the library had worked quite efficiently as a screening tool."

Current efforts are aimed at increasing the number of human genes targeted by the library, said the researchers. They emphasized that the current and future libraries will be made available to the research community at a nominal cost through Open Biosystems, Inc., in Huntsville, AL.

"For the first time this gives us the opportunity to do a version of forward genetics in mammalian cells -- where we can look at hypomorphic mutations, ranging from mild to severe, and their consequences on phenotypes, on what will eventually evolve to a genome-wide scale," said Hannon. "Thus, these libraries will evolve into an important resource for the research community."

Source: Howard Hughes Medical Institute

post Posted: Mar 28 2004, 04:49 PM
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