Monthly Archives: March 2014

A strategy to genetically modify cells from people infected with HIV could become a way to control the virus that causes AIDS without using antiviral drugs, according to results from an early-stage trial that were published on Wednesday.

Data from the small study of the Sangamo BioSciences therapy, known by the code name SB-728-T, were issued in the New England Journal of Medicine, the first publication of data from a human trial of a technology called "gene editing."

The technique is designed to disrupt a gene, CCR5, used by HIV to infect T-cells, the white blood cells that fight viral infections. A patient's cells are removed and processed to alter the DNA that codes for the CCR5 receptor. The altered cells are multiplied and tested, then infused back into the patient.

The Phase 1 trial, led by the University of Pennsylvania, enrolled 12 HIV patients. The study's main goal was safety, but it also showed that the modified T-cells persisted and the presence of HIV DNA decreased, the researchers said.

"It's very solid, elegant science," said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "There is a strong suggestion that cells that are generated are less susceptible to dying."

Sangamo plans to release more trial results this week in Boston at the Conference on Retroviruses and Opportunistic Infections. It will also discuss strategies to improve patient outcomes.

The gene editing technique seeks to mimic the resistance to HIV observed in the small number of people who have inherited CCR5 mutations from both parents. A patient in the trial who carried a naturally occurring mutation in one copy of the CCR5 gene saw the presence of HIV drop to undetectable levels.

"The target we are going after, CCR5, is the most advanced and most promising approach for a functional cure for HIV," said Sangamo Chief Executive Officer Edward Lanphier.

The human immunodeficiency virus, or HIV, surfaced more than 30 years ago and now infects more than 34 million worldwide. Prevention measures have helped check its spread, while early detection and new antiretroviral drugs can control the disease for decades, meaning it is no longer a death sentence.

But the complexity of the virus has stymied scientists seeking a cure. Antiviral drugs are less than ideal due to factors including cost, side effects and drug resistance.

Excerpt from:
Gene therapy may control HIV without drugs

PUBLIC RELEASE DATE:

5-Mar-2014

Contact: Shawna Williams shawna@jhmi.edu 410-955-8632 Johns Hopkins Medicine

Johns Hopkins researchers say they have found one way that a recently discovered genetic mutation might cause two nasty nervous system diseases. While the affected gene may build up toxic RNA and not make enough protein, the researchers report, the root of the problem seems to be snarls of defective genetic material created at the mutation site.

The research team, led by Jiou Wang, Ph.D., an assistant professor of biochemistry and molecular biology and neuroscience at the Johns Hopkins University School of Medicine, reports its finding March 5 on the journal Nature's website.

Two years ago, researchers linked the gene C9orf72, named for its location on the ninth human chromosome, to amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, and to frontotemporal dementia (FTD).

In ALS, motor neurons nerve cells that carry messages from the brain to muscles degenerate and eventually die, which gradually paralyzes the patient. In FTD, neurons in the frontal and temporal lobes of the brain die. Some scientists think the same genetic and biological processes cause both disorders, but with very different symptoms, depending on where in the brain they occur.

The mutation in C9orf72 is called a hexanucleotide repeat expansion, a six-letter "word" of DNA repeated over and over, in a part of the gene that doesn't contain instructions for making any proteins. Although it's normal to have up to 20 such repeats, some people with ALS or FTD have dozens or even hundreds of them. Studies show the mutation is likely responsible for 4 to 8 percent of cases of sporadic ALS the kind that isn't necessarily hereditary and, in some groups, up to 40 percent of the kind that is.

To learn how the repeated sequence causes disease, the Johns Hopkins scientists looked at the structure of the DNA that makes up the gene and the RNA that carries its instructions. Although DNA and RNA are generally seen as long strands, they can bunch and curl to make 3-D structures.

Working with DNA and RNA they made that bore the six-letter "word" repeat, the researchers figured out that both were forming structures called G-quadruplexes. In these formations, guanines called "G" for short, one of the letters in the repeating DNA "word" link up, making stacks that stick together like tiny shelves. The RNA also forms other shapes in the repeating section hairpins and bulges. The researchers speculate that the G-quadruplexes and other structures might be getting in the way of the nucleic acids' normal functions.

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ALS-linked gene causes disease by changing genetic material's shape