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Author Topic: Vaccines Gene Therapy update - articles on gene and vaccine tech  (Read 2533 times)

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Offline bimazek

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"HIV RNase H natural product inhibitors"
NIH Awards HIV Grant to New Consortium
Apr 19 2007, 12:32 PM EST

The NIH selected Millenia Hope, the University of Pittsburgh, and Rutgers University to be a part of a project related to HIV therapeutics. The consortium will receive more than $4.6 million over the next five years.

The project, "HIV RNase H natural product inhibitors", seeks to develop novel HIV treatments directed at the RNase H that will be effective against viral strains that are resistant to current drugs.

The RNase H viral target is essential for HIV-1 replication, but there are no drugs against it in current clinical development, according to Millenia Hope. The company’s Phytomics technology will be used for the production and isolation of plant cell culture-derived natural products to inhibit HIV RNase H.

"This project has an excellent probability of discovering new HIV therapeutics,” states Michael A. Parniak of Molecular Genetics & Biochemistry at the University of Pittsburgh and principal investigator of this program. “The research team we have assembled is worldclass, and Millenia Hope's Phytomics technology provides not only a unique but a readily renewable resource for the discovery and production of novel HIV drugs."

Progress in HIV Vaccines

John Henessey, Jr., Ph.D., senior director of bioprocess and bioanalytical research at Merck Research Laboratories (Whitehouse Station, NJ) identified the three major challenges for HIV vaccine R&D: the diversity of the target population; the diversity in amino acid sequence between different clades of the HIV virus; and issues related to vaccine supply, demand, and delivery.   The Merck HIV vaccine is a replication-incompetent adenovirus type 5 construct that is E1 deficient and propagated in an E1-complemented PER.C6 cell line. It incorporates transgenes for gag, pol, and nef, which produce the corresponding proteins when taken up by host cells, inducing an immune response to the virus.

Boro Dropulic, Ph.D., founder and CSO of VIRxSYS (Gaithersburg, MD), presented the company's work using lentiviral-based vectors for HIV gene therapy. VRX496 is the firm's lentiviral vector expressing a 937-base antisense insert that targets the HIV envelope protein.   The company reported greater than 94% transduction of T lymphocytes in preclinical studies and greater than 100-fold inhibition of HIV replication and is currently completing a Phase I safety trial in HIV-infected patients who have failed at least two regimens of highly active anti-retroviral therapy (HAART).

http://www.genengnews.com   quotes from various articles that mention HIV in gene news

DNA sequencing is a powerful technique firmly entrenched into every aspect of biological research and drug discovery. Recent advances in high-throughput capillary sequencing combined with the shotgun method of sample preparation made sequencing of the whole human genome a reality.

Sequencing of whole genomes leads to identification of novel genes that may influence development of human diseases, enable pathogens to avoid cellular defenses, or make some viruses lethal. Sequencing of the same genes across the population maps polymorphisms that may correlate with susceptibility to certain diseases or with adverse reaction to certain medications. Sequencing of individual genomes may some day become a part of routine medical care, as the therapies will be tailored to a specific genetic profile.

Oligos Enable New Classes of Therapeutics  Replicor is developing a broad-spectrum, oligonucleotide-based antiviral compound that has potential as a prophylactic and therapeutic agent in case of an influenza pandemic. It also has the potential to become a potent weapon against drug resistant viruses (like HIV) and for certain viral infections like hepatitis C, where there are large unmet medical needs.
Archemix is developing aptamers through the in vitro selection of nucleic acids. "We like to call them chemical antibodies," notes Markus Kurz, Ph.D., associate director of chemistry, because they offer the protein-to-protein blocking interactions of antibodies and the ease of chemical synthesis. "It's the best of both worlds," he says.   Mode of action of double-stranded DNA decoy oligonucleotides (decoy ODNs). The individual steps represent the following processes: 1. Ligand binding and receptor activation, 2. Transcription factor activation and dimerization, 3. Transcription factor translocation into the nucleus, 4. Initiation of gene transcription, 5. Cellular uptake of decoy ODNs, 6. Competitive biding of decoy ODN to transcription factor, 7. Inhibition of gene transcription.   


Rothberg, Ph.D., founder and chairman of 454 Life Sciences, believes that the company’s technology will create the same ripple effect in the life sciences as the introduction of PCs created in the computer industry. "Our single instrument generates the same amount of data as 100 capillary sequencing machines." Therefore, a $500,000 investment in our Genome Sequencer replaces a $30-million investment in the sequencing instruments and a $20-million investment in the supporting robotics.   Other applications in development include identification of signaling pathways responsible for cancer resistance, drug-resistant HIV isolates, microRNAi, and expression profiling. "Even though the impact on medical research is still to be understood, 454 brings us a step forward toward a visionary goal of $1,000 genome sequencing,"

Working in nanoscale drastically reduces the preparation time, handling, inventory, and storage costs associated with the traditional whole genome sequencing approaches. The 454 technology does not require subcloning, bacterial propagation, or handling of individual clones. The whole genome is nebulized, and the library is subjected to several enzymatic steps, followed by ligation to the specialized adaptors. The library is fractionated, and the individual fragments are captured on Sepharose beads. Each captured molecule is PCR amplified on the bead within a droplet of the buffer (microreactor) suspended in an oil emulsion. This unique miniaturization approach generates approximately 1,000 microreactors per microliter.  DNA-carrying beads are arrayed in the wells of the fiber-optic slides, and the individual fragments are sequenced all at the same time. "This is like moving from a vacuum tube to a transistor," says Dr. Rothberg. "We have no limits on the problems we can solve. It is a disruptive technology."

Renewed interest and funding for flu vaccine strategies will have to share center stage with ongoing R&D efforts on a variety of vaccine targets including the continuing focus on HIV vaccines, immunotherapeutic-based cancer vaccines, infectious targets with the potential for bioterrorism, and vaccines against common infectious agents such as human papillomavirus (HPV).  A clinical study recently published in The Lancet (364:1757-1765) demonstrated the effectiveness of a vaccine against HPV in reducing the prevalence of cervical cancer. The vaccine targets the two most common types of cancer-causing HPV, HPV-16 and HPV-18, and was effective against 95% of persistent HPV infections among the study participants who received at least one dose of the vaccine. http://www.genengnews.com/articles/chitem.aspx?aid=863

all hiv articles

HIV exemplifies the time-consuming and difficult nature of vaccine discovery. HIV has one of the highest mutation rates known, resulting in a virus with significant genetic diversity, a major impediment toward vaccine development. The nine subtypes (clades) within the HIV M group can differ by more than 10% within clades and 30% between clades. Therefore, even if a vaccine is proven effective for a specific clade, it is uncertain that the protection would extend to other strains within the clade and across different clades. This raises the question of whether several vaccines are needed to offer protection against each of the distinct viral variants. As CD8+ T cells have been shown to play an important role in containing HIV infection, vaccine development has focused on the biological mechanism of CD8+ T-cell responses upon HIV infection.

Virxsys (www.virxsys.com) raised a total of almost $52 million in 2006 financings.

So, in addition to exciting technology, what does it take to raise money in the gene therapy space? I believe there are several key factors that a gene therapy company must have, including an effective technology and market positioning, the capacity to manufacture the product, and professional fundraising assistance by a qualified placement agent.

Virxsys is developing a lentiviral vector gene delivery technology that will initially be applied to HIV/AIDS. During its recent fundraising round, having effective technology and market positioning in place impressed many potential investors and was a key to attracting their support. Additionally, lack of manufacturing capability and capacity can hinder advancement through clinical trials and product commercialization. Sophisticated investors understand this and want to know a target company can overcome these challenges before investing large sums of money. 

When it comes to biotechnology innovation, gene therapy and genetic medicine led the way in the early and mid 1990s. The concept of gene therapy was viewed as the arrival of tomorrow’s medicine today. The excitement surrounding the first gene therapy trials were the catalyst for creating regulatory bodies at the NIH and other agencies. It appeared gene therapy was ready to change the face of medicine.

Then clinical events and other developments (most notably the death of a patient at the University of Pennsylvania in 1999) precipitated an industry-wide moratorium on this exciting and potentially promising area of research. There was heavy criticism of the technology and many people began to doubt whether gene therapy would ever achieve its potential. Since then we have learned a great deal and have refined the technology to the point that the use of gene therapy for the treatment of serious diseases is once again a realistic possibility in the foreseeable future.

Offline Zanarkand

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Re: Vaccines Gene Therapy update - articles on gene and vaccine tech
« Reply #1 on: April 20, 2007, 08:12:38 PM »
Can someone please summarize this for meee? ^_^
All Your Base Are Belong To Us


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