My 100th Post: Marligen Makes a Deal

It’s been a while since I’ve heard anything about Marligen, the only Biotech company in my home town of Ijamsville. And even though they are less than a mile from the Montgomery County line, they’re still a FredCoBio member. That’s like having a semi-sterile cell culture flask, I guess. Here’s the news clip, via businesswire.com:

Marligen Exclusively Licenses Genisphere Labeling Technology for the Detection of microRNAs on the xMAP® Platform

Marligen Launches Vantage™ Line for the Purification, Labeling and Detection of microRNAs

IJAMSVILLE, Md.–(BUSINESS WIRE)–Marligen Biosciences, Inc., a supplier of innovative products for the life sciences research market, will become the exclusive provider of Genisphere’s biotinylated labeling kits for detection of microRNAs on the xMAP^® multiplex platform. The microRNA labeling kits using Genisphere Inc.’s 3DNA^™ dendrimer signal amplification technology will be an integral product to Marligen’s new offering supporting researchers studying microRNAs. The Vantage™ product line includes reagent kits for purifying, labeling and detecting microRNA species.

Genisphere’s unique 3DNA^™ dendrimer technology is based on highly branched DNA structures serving as scaffolds for multiple biotins. The use of Genisphere’s signal amplification technology in combination with the Vantage™ microRNA detection panels offers researchers a fast and cost-effective system to directly profile multiple microRNAs in a single sample. The complete system offers exceptional sensitivity and throughput capabilities of greater than 100 samples in a single day and is compatible with total RNA or enriched RNA including degraded RNA from archived tissues. The initial Vantage™ microRNA Detection Panels are designed for profiling the relative abundance of different microRNA species known to be relevant in oncology. The Vantage™ Products will be launched at the upcoming annual meeting of the American Association of Cancer Research.

“High throughput profiling of MicroRNAs presents a challenge when combining rapid, effective labeling with improved detection sensitivity,” said Dr. Robert Getts, Director of R&D at Genisphere. “The complete Vantage™ package, having integrated our rapid 3DNA™ dendrimer microRNA labeling method with Marligen’s carefully designed detection panels, provides an optimized solution with consistent performance and much needed sensitivity on the xMAP® high-throughput detection platform.”

“Because microRNA play such an important role in tumor development and progression, it is vital we offer researchers innovative tools that allow them to profile these biological markers in archived samples. Our collaboration with Genisphere allows us to provide one of the most rapid and sensitive methods to screen directly from such samples,” said James Lazar, Chief Scientific Officer of Marligen Biosciences. “This will not only advance basic research but should expedite the application of microRNA detection in the diagnosis of cancer.”

It’s strange, because this article couldn’t be more timely. The Founder & CEO, Sherry Challberg, was the one who hired me in April 1988 to move South to Maryland. It’s hard to believe that it has been 20 years ago to this day.

I was working in a lab at the University of Rochester doing papilloma virus research (which supported research leading to a Nobel prize for Micheal Bishop in 1989 and in support of research into Open Reading Frames, which lead to the 1993 Nobel Prize for Sharp & Roberts and also 1989 Nobel prize in Chemistry for Thomas Cech’s discovery of Ribozymes) and steroid hormone modulation of gene expression (in support of research into Protein Phosphorylation as a regulatory mechanism of proteins leading to the 1992 Nobel prize for Edmund Fisher and Edwin Krebs and leading to the discovery of COX-2 enzyme and COX-2 inhibitors in 1991 which was subsequently “borrowed” by Pfizer and made into the blockbuster drug Celebrex, reaffirming Dr Young’s assertion that I was leaving academia to go work in the “Evil Empire” that is Industrial research).

But enough name dropping, lest you think this blog is just about shameless self-promotion.

Back to the story. We moved down here in 1988 to work in the Molecular Diagnostics Division of Life Technologies. This was sold in 1990 or ‘91 to become Digene. To the left you see the 25 year old version of yours truly, pretending I am doing lab work. This is from the front page of the Baltimore Sun’s Business section on Dec. 21, 1988. The story was about our pending FDA approval for (one of?) the first clinically approved DNA test on the market. You may notice that the paper has a tinge of orange from age, and if you look closely, you’ll see my beard was still orange, too. By the way, the Dow closed at a mere 2,166 that day, a 1-year CD would yield 9.00 % and the Prime was 10.5%.

ImQuest in Mississippi

I just found it funny that this PR Newswire press release was picked up by the SunHerald, covering Southern Mississippi. It’s a nice write-up, but not sure I’d like to go all of the way to Delhi to have to present it!

ImQuest Scientists Present Important HIV Microbicide Development Results at Microbicides 2008 in Delhi, India

By ImQuest Life Sciences

FREDERICK, Md., April 8, 2008 –

ImQuest scientists Robert W. Buckheit, Jr., Ph.D. and Karen M. Watson, M.S. presented the results of studies performed with products licensed by ImQuest Life Sciences, Inc. at the recent Microbicides 2008, an international conference held in New Delhi, India and attended by microbicide scientists, developers, and care givers from around the world. Dr. Buckheit was invited to speak by the Conference organizers, presenting the results of ImQuest’s current research on the pyrimidinedione series of microbicide candidates in a special symposium entitled “New Approaches to Microbicide Candidates”. ImQuest is currently developing the highly unique, dual acting pyrimidinediones as potential microbicide candidates based on their significantly high potency against HIV-1, their unique mechanism of action, and their ability to potently suppress the sexual transmission of wild type and drug resistant viruses.

According to Dr. Buckheit (Executive Vice President and Chief Scientific Officer of ImQuest Life Sciences, Inc., and President of its subsidiary, ImQuest BioSciences, Inc.), “It was highly gratifying to speak on our novel pyrimidinedione products at this Conference and to have them recognized as a new approach to HIV prevention by the thousands of dedicated people leading these efforts around the world.” ImQuest has obtained funding from the National Institutes of Health and The International Partnership for Microbicides to further develop these products.

At the conference, Ms. Watson (Manager, Topical Microbicide Research and Development) presented three papers, including additional data on the pyrimidinedione IQP-0528, newly emerging data on the microbicide candidate ISIS 5320 (IQP-0831), and results from laboratory studies performed using ImQuest’s recently developed Microbicide Transmission and Sterilization Assay which quantifies the ability of microbicide products to completely suppress the sexual transmission of HIV.

ImQuest Life Sciences, a privately held U.S. company located in Frederick, Maryland specializes in the preclinical and clinical development of novel compounds for the treatment of infectious disease and cancer. ImQuest BioSciences, also located in Frederick, Maryland, is a leading provider of anti-infective and anti-cancer drug and vaccine development services to the biotechnology and pharmaceutical industry. Both companies are highly involved in efforts to develop an effective anti-HIV topical microbicide.

DNA vaccine delivery program at NCI

I was reading an interesting bit this morning about a collaboration between scientists at NCI-Ft Detrick and Inovio Biomedical Corp. of San Diego, CA. The program, initiated in July 2007, is being conducted under a Cooperative Research and Development Agreement (CRADA) and will assess novel HIV constructs in non-human primates, cytokine genes as vaccine adjuvants (immune system stimulants), and possibly anticancer therapies delivered using Inovio’s electroporation-mediated DNA delivery technology. The work is being performed in collaboration with Drs. George Pavlakis and Barbara Felber at the Fort.

The method of electroporation is a “needle-less” vaccine, introducing the vaccine via electronic pulses through the skin or soft tissue. There are some analogies for BioElectronics mechanisms, as well as standard electroporation methods used in recombinant DNA technology like electro-competent cells.
Here’s a little more from Inovio’s web site:

In all of these applications, the purpose of electroporation is to assist the uptake of useful molecules such as DNA vaccine into a cell. The biological material is first injected into or applied to the surface of the target tissue and followed by the application of brief, controlled electrical pulses directed to that tissue. As shown in the pictures below, electroporation’s millisecond electrical pulses temporarily create enhanced permeability of pores in the cell membrane. After a short period of time the pores reseal, leaving the cells undamaged. During the period that these pores exist, a significant quantity of the previously injected biomolecules are taken up and then trapped in the cell, enabling them to then perform their intended function.

How does the electroporation process work?

The following illustration depicts the process of administering a DNA vaccine using electroporation:

Inovio’s electroporation technology can increase the cellular uptake (also termed transfection) of an agent by 1,000 times or more. When used to deliver DNA vaccines, Inovio’s systems can increase levels of gene expression (i.e. production of the coded protein) by 100 times or more compared to plasmid DNA delivered without other delivery enhancements.

What results have been achieved using electroporation-based DNA delivery?

Learn about Inovio’s DNA delivery systems.

Genome Projector

I ran across this neat little tool called the Genome Projector via My BioTech Life. It’s a Google Maps based graphics program which contains 320 bacterial genomes and gives you a zoomable view of circular DNA sequences, pathways and a DNA walk. It’s pretty cool and I’ll link it in the Gene Jockey section later. Why don’t you give it a try?

PCR Video

No, this is not an instructional video, rather an add produced by BioRad. Wow, it doesn’t get any geekier than this:

It kind of makes you wonder why you watched the whole thing, doesn’t it?

This one is fascinating and worth the watch.  If they can pull 1/2 this off it would be amazing (thanks to Amniopop)

Frederick Team Discovers new Breast Cancer Marker

This news just flashed across the wire, from the Sloan-Kettering Cancer Institute site:

Researchers Identify New Genetic Marker for Breast Cancer

March 3, 2008

NEW YORK, NY - An international group of investigators led by scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) and the National Cancer Institute has identified a new genetic marker of risk for breast cancer. Women with this DNA variation are at a 1.4 times greater risk of developing breast cancer compared to those without the variation. The findings are to be published online on March 3, 2008 in the journal Proceedings of the National Academy of Sciences.

“These results are exciting because they point us to new molecular pathways that may be associated with breast cancer,” said the head of the research team and the study’s senior author, Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at MSKCC.

The study used a methodology called genome-wide association mapping, which looks at genetic variations across the entire genome that alter the individual building blocks of DNA makeup. These alterations may occur more frequently in individuals who have certain types of disease than in carriers without such disease. In this study, a new gene locus, a specific place on a chromosome where a gene is located, was associated with breast cancer risk. That gene locus is on the long arm of chromosome 6.

“These research findings are of great interest because of the method of genome- wide association used to discover this new locus as well as others in recent months,” said Bert Gold, PhD, a Staff Scientist at the National Cancer Institute in Frederick, MD., and first author of the current study.

While the risk associated with this genetic marker is much lower than that of BRCA genetic mutations for example, this discovery will increase the understanding of the genetic variants that contribute to breast cancer.

“These results are exciting because they point us to new molecular pathways that may be associated with breast cancer.” – Kenneth Offit, MD, MPH, study’s senior author and Chief of the Clinical Genetics Service at MSKCC

Researchers used samples largely from MSKCC, but also from other sites in the US, Canada, and Israel. Participants were all of Ashkenazi (Eastern European Jewish) ancestry. The study used a three-phase design centered on 249 families with multiple cases of breast cancer and no mutations of the BRCA genes.

“This newly identified genetic marker will not have any immediate clinical implications or impact on current screening guidelines for familial breast cancer,” said Dr. Offit. “As such, a test for these markers is not available to the general public and these tests should be performed only as part of research studies.”

Dr. Offit’s research team is now confirming that this risk marker is observed in other populations, and is studying possible changes in two genes in the chromosome 6q region.

The study was funded in part by federal funds from the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, the Breast Cancer Research Foundation, the Susan Komen Foundation, the Lymphoma Foundation, and the Niehaus, Southworth, Weissenbach Cancer Research Fund.

Good Stuff from NCI

I ran across an article the other day on the NIH web site about a break through discovery made by a group in Frederick.

Just a cut and paste from the NIH web site:

Scientists Find Antibody that Can Potently Neutralize Two VirusesIn laboratory experiments, scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and their colleagues supported by the NIH National Institute of Allergy and Infectious Disease (NIAID), have discovered an antibody that neutralizes two viruses classified as henipaviruses. Nipah virus (NiV) and Hendra virus (HeV) are highly infectious agents that transitioned from infecting flying foxes in the mid-1990s to causing fatal disease in humans and livestock in Australia, Bangladesh, India, Malaysia, and Singapore. Recent outbreaks have resulted in encephalitis and acute respiratory distress, person-to-person transmission, and up to 70 percent fatality rates. The finding appears in the Feb. 15, 2008, issue of The Journal of Infectious Diseases.

Antibodies are proteins that are found in blood or other bodily fluids of vertebrates and are used by the immune system to identify and neutralize foreign molecules, including bacteria and viruses. According to study author Dimiter S. Dimitrov, Ph.D., of NCI’s Center for Cancer Research in Frederick, Md., “We hope that with further research this antibody can save human lives. The insights offered about how it works also could potentially provide a starting point for the development of tools for targeting other diseases.”

The first step in countering infections caused by these viruses is to find antibodies that can neutralize them. Viral neutralization is the process by which an antibody alone or an antibody plus another molecule, called complement, block the infectivity of a virus. Zhongui Zhu, Ph.D., of Dimitrov’s group and their NIAID-supported collaborator Christopher Broder, Ph.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md., had previously identified antibodies to NiV and HeV by panning a large antibody library against a soluble form of the protein that makes up the HeV shell. One of these antibodies, m102, exhibited a strong ability to neutralize both NiV and HeV.

In their current experiment, the researchers created an improved version of m102, called m102.4, by using a complex procedure called in vitro maturation. The m102.4 version is even more potent than its parent antibody, m102, and can neutralize both HeV and NiV without a loss of cross-reactivity, which is the ability of an antibody that is specific for one target, or antigen, to bind to a second antigen. The researchers believe that the m102.4 clone is the first fully human antibody that is capable of potently neutralizing both HeV and NiV. Their results suggest that m102.4 may prove useful as a therapeutic for treatment of diseases caused by henipaviruses. Their initial experiments in small mammals called ferrets found that m102.4 was well tolerated, exhibited no adverse effects, and retained high neutralizing activity, which may point to this antibody’s potential for clinical use as a preventive agent, a diagnostic probe, or an antiviral therapeutic.

“The generation of a potent antibody against both HeV and NiV could help control outbreaks in geographical regions susceptible to henipaviruses, and result in a benefit for mankind,” said Dimitrov. He also noted that the laboratory technology they used for the maturation of antibodies is being used for the development of antibodies against cancer.

This study was a collaboration with investigators Katharine N. Bossart, Ph.D., and Lin-Fa Wang, Ph.D., from Geelong, Victoria, Australia, where there is a high-level safety and security facility for testing the antibody.

For more information on Dimitrov’s laboratory at CCR Frederick, please go to http://ccr.cancer.gov/staff/staff.asp?profileid=5749.

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference:
Zhu Z, Bossart K, Bishop KA, Grameri G, Dimitrov AS, McEachern JA, Feng Y, Middleton D, Wang L, Broder CC, Dimitrov DS. Exceptionally Potent Cross-Reactive Neutralization of Nipah and Hendra Viruses by a Human Monoclonal Antibody. The Journal of Infectious Diseases, February 15, 2008.

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Mammalian Protein Localization Database

I found a write up in this week’s Genetic Engineering News about a web site from Australia that provides an interactive guide to the subcellular location of proteins.  I think it’s a pretty neat tool and will be add this to the Gene Jockey section momentarily.

Genetic Characterization of Feline Leukemia Virus from Florida Panthers

I ran across an interesting bit of research this morning while surfing. An article in the CDC Publication “Emerging Infectious Diseases”, authored by Meredith A. Brown, from NCI and Stephen J. O’Brien, SAIC-Frederick et al.

The suggested citation: Brown MA, Cunningham MW, Roca AL, Troyer JL, Johnson WE, O’Brien SJ. Genetic characterization of feline leukemia virus from Florida panthers. Emerg Infect Dis [serial on the Internet]. 2008 Feb [date cited]. Available from http://www.cdc.gov/EID/content/14/2/252.htm

Being in industry for the past 20 some odd years, I am not real hip on current publications and don’t even subscribe to PubMed. I get a lot out of the abstracts and turn to my more research-minded partners if I need to pull up a publication.

Here’s the abstract

Abstract
From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were most similar to the well-characterized FeLV-945 strain, which is highly virulent and strongly pathogenic in domestic cats because of unique long terminal repeat and envelope sequences. These unique features may also account for the severity of the outbreak after cross-species transmission to the panther.

Does anyone know if there is a central site for Publications coming out of NCI, NIAD, SAIC or any of the other Agencies at Ft Detrick? Drop me a line if you do. This is the kind of research I would like to give more publicity to in my little space on the web.

And don’t forget to check out the entire Calendar of seminars, all open to the public, hosted by NCI. I’ll stick them on the Calendar page since it’s a pretty long list.

SuperArray Makes a Splash

And I almost missed it. The story broke on Friday, but didn’t make a splash locally.

They have licensed a technology through Carnegie Institute which allows SuperArray to theoretically silence every gene in human, mouse and rat genome. Pretty damn powerful if it works as billed.

Kudos to Paul Nisson (former Life Technologies and University of Rochester colleague) and everyone at SuperArray (Fred. County Incubator Company of the year in 2006)!

Here are a few of the links:

Yahoo!Finance

GenomeWeb Daily

Genetic Engineering News

PharmaLive

IP Today