The United States government has approved the first drug produced by genetically engineered livestock. ATryn, the drug meant to prevent fatal blood clots in people with a rare condition, is a protein extracted from the milk of goats that have been given a human gene. The drug is the first to have been cleared by the United States Food and Drug Administration (FDA) under guidelines the agency adopted recently to regulate the use of transgenic animals in the nations drug and food supply.

GTC Biotherapeutics produces ATryn from a herd of 200 goats that live under quarantine on a high-security farm in central Massachusetts. The goats were bred to contain a human gene that causes their milk to produce a human blood protein, antithrombin, that can be extracted and processed into the anti-clotting drug. Such animals could become a way of producing biotechnology drugs at lower cost or in greater quantities than with the existing methods.

GTC Biotherapeutics said one of its goats can produce as much antithrombin in a year as can be derived from 90,000 blood donations. To make its protein, GTC took the human gene for antithrombin and linked it to goat DNA that normally controls production of a protein found in milk. That ensured that the protein would be produced only in the milk. The gene was injected into a one-celled goat embryo, which was then implanted into the womb of a surrogate mother. The goat with the gene that produced antithrombin in its milk, the founder animal, was then mated with others through conventional breeding to start a herd.

A Dutch company, Pharming, plans to apply for United States approval of a drug produced in the milk of transgenic rabbits to treat hereditary angio-oedema, a protein deficiency leading to dangerous swelling of tissues. Another company, PharmAthene, working under a United States Defence contract, is developing a treatment for nerve-gas poisoning in the milk of transgenic goats.

Many of the newer protein-based drugs, such as the cancer drugs Avastin and Erbitux and the arthritis drugs Enbrel and Humira, are produced in genetically engineered Chinese hamster ovary cells that are grown in big stainless-steel vats. But a cell culture factory can cost hundreds of millions of dollars to build. Using livestock eliminates all that steel and shrinks the investment to tens of millions of dollars, said Mr. Geoffrey Cox, CEO of GTC.

Source: greenbio.checkbiotech.org

In a new study at the University of California Los Angeles (UCLA), the United States, researchers were able to generate functionally mature motor neurons from induced pluripotent stem (iPS) cells, which are engineered from adult somatic cells and can differentiate into most other cell types. This study is the first to use human iPS cells to generate electrically active motor neurons, a key hallmark of functional maturation that is essential for any future application of iPS cells.

The UCLA Broad Stem Cell Research Centre research team of Dr. William Lowry, Dr. Bennett Novitch, Dr. Harley Kornblum and Dr. Martina Wiedau-Pazos compared the ability of different human cell lines to generate motor neuron progenitors and fully differentiated motor neurons. When measuring the electrophysical properties of the iPS-derived neurons, the researchers found that the iPS cells followed a normal developmental progression to form mature, electrically active neurons. Dr. Lowrys team used skin fibroblasts and reprogrammed them back into an embryonic state, with the ability to differentiate into any cell type in the human body. They then took those cells and differentiated them into motor neurons.

The study demonstrated the feasibility of using iPS-derived motor neurons and their progenitors to replace damaged or dead motor neurons in patients with certain disorders. It also opened the possibility of studying motor neuron-related diseases in the laboratory to uncover their causes.

Source: www.sciencedaily.com

Research by Dr. Marija Balic from the Medical University in Graz, Austria, and her colleagues suggests that a new technique to determine tumour methylation status can be used in archived tissue samples. The report is published in the Journal of Molecular Diagnostics.

DNA in tumours is often altered compared with DNA in normal tissues. One common DNA alteration in cancerous tissue is hypermethylation, which results in loss of gene expression. The difference in methylation between normal and cancerous tissues can be used as a biomarker for early cancer diagnosis, risk assessment and response to therapy. Archival tissues, or tissues that are formalin-fixed and paraffin-embedded for long-term storage, are however difficult to screen for cancer biomarkers due to the low quality of their DNA. It is therefore important to develop new techniques to screen for DNA methylation that can be used in archival tissues.

Dr. Balic and colleagues examined the ability of high-resolution melting analysis (HRM) to detect methylation on archival tissues from colorectal cancer patients. They found that HRM provided similar results for both archival and fresh tissues. In addition, they validated the results using the widely used MethyLight assay. Most importantly, the reported method has the potential to make DNA methylation analysis possible on tissues that have undergone formalin fixation and paraffin embedding, the most common means of tissue storage, thus enabling analysis of this vast tissue resource.

Source: www.eurekalert.com

In the United States, researchers at the Dana-Farber Cancer Institute (Dana-Farber), Burnham Institute for Medical Research (Burnham) and the Centres for Disease Control and Prevention (CDC) report the identification of human monoclonal antibodies (mAb) that neutralize an unprecedented range of influenza A viruses, such as avian influenza (H5N1) virus, previous pandemic influenza viruses, and some seasonal influenza viruses. The antibodies identified bind to the highly conserved stem region of H5 type hemagglutinin (HA), instead of its highly mutable head portion. Binding to the stem prevents a conformational change in the protein that is necessary for viral entry into the host cell, thereby preventing further infection. In the study, the scientists used a human antibody phage display library to identify 10 mAb that bind to the stem of H5 type HA, the influenza protein responsible for viral entry into the host cell. They determined the X-ray crystal structure of the mAb bound to the H5N1 HA, which showed that the heavy chain of the mAb inserts into a highly conserved pocket in the HA stem, inhibiting the conformational change required for membrane fusion and viral entry into the cell. The scientists further showed that an unprecedented number of different types of bird flu and seasonal influenza viruses were inhibited and the mAb protected mice that were exposed to H5N1 virus.

Source: www.eurekalert.org

A new study has revealed the molecular mechanism of how a protein determines the fate of the cells that make and release insulin. Dr. Michael Lan Professor of Paediatrics and Genetics at Louisiana State University Health Sciences Centre, the United States, and the senior author of the study and colleagues are studying INSM1, a protein involved in the regulation of endocrine cells. INSM1 plays a critical role in the development of pancreatic beta cells the only cells in the body that secrete insulin. Beta cells are located in islet cell clusters throughout the pancreas.

Diabetes mellitus type 1 results from the destruction or dysfunction of islets and their beta cells. Type 2 diabetes results from the bodys inability to use insulin properly and a gradual decrease in the ability of pancreas to make it. The scientists used pancreatic cancer cells to investigate the effects of INSM1, a transcription factor, on cell cycle function. They developed an inducible system to turn on INSM1 in pancreatic cancer cells and found that it resulted in a significant reduction in the cells growth rate. They showed that the mechanism for this growth inhibition was due to an interaction between INSM1 and cyclin D1, an important cell growth promoting protein. The interaction between these two proteins impaired the growth of the tumour cells. Further, transplantation of INSM1 on pancreatic tumour cells into mice showed the growth rate of these tumour cells was greatly inhibited compared with the control cells.

Source: www.medicalnewstoday.com