Posts Tagged ‘gene therapy’

Moving gene therapy one step closer to clinical reality

 :: Posted by American Biotechnologist on 04-05-2011

Scientists from the Morgridge Institute for Research, the University of Wisconsin-Madison, the University of California and the WiCell Research Institute moved gene therapy one step closer to clinical reality by determining that the process of correcting a genetic defect does not substantially increase the number of potentially cancer-causing mutations in induced pluripotent stem cells.

Their work, published in the online edition of the journal Proceedings of the National Academy of Sciences and funded by a Wynn-Gund Translational Award from the Foundation Fighting Blindness, suggests that human induced pluripotent stem cells (iPS) altered to correct a genetic defect may be cultured into subsequent generations of cells that remain free of the initial disease.

However, although the gene correction itself does not increase the instability or the number of observed mutations in the cells, the study reinforced other recent findings that induced pluripotent stem cells themselves carry a significant number of genetic mutations.

In brief, scientists produced iPS cells by episomal reprogramming, corrected a disease-causing mutation by homologous recombination and removed the puromycin cassette that was used for gene selection using Cre recombinase.

Results of the study indicate that both homozygous recombination and cassette removal did not increase the iPS mutational load. Nonetheless, the initial induction of primary dermal fibroblasts into iPS cells lead to a fairly substantial mutational load at the time of derivation.

This study is important in that it demonstrated that downstream cloning events do not introduce further mutations into iPS cells which can be a source of tremendous therapeutic value. Nonetheless, it is important for further studies to focus on reducing mutational events caused by iPS induction which may be a serious drawback to introducing iPS therapy into the clinic.

Sources:

Howden S et al, (2011) Genetic correction and analysis of induced pluripotentstem cells from a patient with gyrate atrophy. PNAS

and

Wisc

Gene Therapy Helped Young Boy Recover His Eyesight

 :: Posted by American Biotechnologist on 05-05-2010

Sometimes working at the bench can be tedious and frustrating. Preparing samples, running experiments, analyzing data, REDOING experiments (ugh!)… And what is all the hard work for? To “further science?” To be rich and famous? Here’s a video that we’ve discovered that will put a tear in your eye and pride in your heart. Way to go biotechnologists!

Closing in on a Cure for Stressed-Out, Overweight Individuals

 :: Posted by American Biotechnologist on 04-21-2010

As I sit here munching on a sugar laden donut and occasionally pacing back and forth anxious about my upcoming physical, I’ve come across a study that confirms what I’ve always suspected: stress is bad for you and can make you fat. Not so impressed? What is impressive, however, is the identification of a single gene that, when upregulated increases anxious behavior and causes metabolic changes common to diabetics. Is it possible that one day soon we will have a therapeutic to prevent stressed out individuals (doesn’t that describe almost all of us) from becoming obese diabetics?

Check out the full story below from the Weizman Institute.

The constant stress that many are exposed to in our modern society may be taking a heavy toll: Anxiety disorders and depression, as well as metabolic (substance exchange) disorders, including obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress. These problems are reaching epidemic proportions: Diabetes, alone, is expected to affect some 360 million people worldwide by the year 2030. While anyone who has ever gorged on chocolate before an important exam understands, instinctively, the tie between stress, changes in appetite and anxiety-related behavior, the connection has lately been borne out by science, though the exact reasons for this haven’t been crystal clear. Dr. Alon Chen of the Weizmann Institute’s Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behavior, but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes. These findings were published online this week in the Proceedings of the National Academy of Sciences (PNAS).

All of the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes the metabolism of various substances and even changes in food preferences. What ties all of these things together? The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved. This protein is produced in certain brain cells — especially in times of stress — and it’s known to play a role in regulating the body’s stress response. These nerve cells have extensions that act as ‘highways’ that speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions — oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including levels of anxiety. Nerve cells in both these areas have special receptors for Ucn3 on their surfaces, and the protein binds to these receptors to initiate the stress response.

The researchers developed a new, finely-tuned method for influencing the activity of a single gene in one area in the brain, using it to increase the amounts of Ucn3 produced in just that location. They found that heightened levels of the protein produced two different effects: The mice’s anxiety-related behavior increased, and their bodies underwent metabolic changes, as well. With excess Ucn3, their bodies burned more sugar and fewer fatty acids, and their metabolic rate sped up. These mice began to show signs of the first stages of type 2 diabetes: A drop in muscle sensitivity to insulin delayed sugar uptake by the cells, resulting in raised sugar levels in the blood. Their pancreas then produced extra insulin to make up for the perceived ‘deficit.’

‘We showed that the actions of single gene in just one part of the brain can have profound effects on the metabolism of the whole body,’ says Chen. This mechanism, which appears to be a ‘smoking gun’ tying stress levels to metabolic disease, might, in the future, point the way toward the treatment or prevention of a number of stress-related diseases.