A team of Washington State University (WSU) researchers, led by Grant Trobridge, an associate professor of pharmaceutical sciences, has recently developed a new and safe way to reduce the risks of gene therapy. They have done so by altering the way the virus carries the beneficial gene to the target cell. The new technique is safe and will prevent triggering proto-oncogenes which assist in cancer tumors.

Gene therapy is an experimental technique whereby scientists technically replace the missing or defective genes with the modified genes to correct genetic disorders. It uses virus vectors — usually retroviruses – to deliver the modified gene to the target cell. Gene therapy is the future and, once available, will be an effective replacement for drugs and surgery for various incurable diseases including cancer and blood disorders.

Cancer is a problematic condition and among the leading causes of death in the world. Nearly 700,000 new cancer cases will be reported in the United States and 600,000 people will die from the disease.

The most common cancers originate in the breast, lung, prostate, colorectal area and the skin.

The uncontrolled growth of cancerous tumors happens when proto-oncogenes are turned on by various environmental and biological factors. Proto-oncogenes are genes that encode for proteins regulating cell growth.

Grant D Trobridge and his colleagues altered the viral gene therapy to target a disease known as SCID-X1, also known as the “Boy in the Bubble Syndrome”. SCID-X1 is a life threatening immunodeficiency disease in the newborn.

Genotoxicity is a major problem of concern during gene therapy and the researchers used a “foamy” retroviral vectors into regions enriched with trimethylated histone H3 at lysine 9. This was done by modifying the viral Gag and Pol proteins.

The researchers used foamy retroviral vectors over gammaretroviral and lentiviral vectors as they are safer and have a lower tendency to activate nearby genes. The vectors are called “foamy” because they have a tendency to form foams under certain conditions.

Trobridge says, “Our goal is to develop a safe and effective therapy for SCID-X patients and their families. We’ve started to translate this in collaboration with other scientists and medical doctors into the clinic.”

The researchers have already carried out clinical trials for SCID-X1 by targeting human cord blood CD34+ cells in Paris and London. 17 out of 20 patients were successfully treated with the retroviral vector gene therapy; however, 5 patients developed leukemia after undergoing the treatment, indicating the need of further improvement in this treatment.

Still, the advantage of retargeted foamy retroviruses is that they can be produced at high titers, more than 107 transducing units/ml are unlikely to target cells which don’t need to be targeted and the modified Gag and Pol helper allows the easy production of therapeutic foamy retroviral vectors.

The study was published in Journal on November 3rd, 2016.

Gene Therapy Can Give People A Chance To Live But Are We Sure It Is Safe?

Gene therapy has risen as a contemporary way to treat diseases, bodily defects and even to enhance our physical and intellectual abilities for better or for worse. It was first carried out in 1990 at the NIH Clinical Center in a four-year old girl with adenosine deaminase ADA deficiency which is a genetic immunodeficiency disease.

Gene therapy has evolved since then but is still complex due to numerous other complications arising by this mode of treatment. An important principle is the Weismann Principle which states that in case of gene therapy, it should be made sure that the modified DNA remains in the body cells and does not appear in the person’s gametes, as this could lead to alterations in the genome that could be passed on to the next generations.

One other hurdle to consider is that a lot of common chronic diseases like cardiovascular disease, diabetes and osteoporosis are caused by multiple altered genes, making it difficult to treat them.

In addition, the body’s immune system can respond negatively to modifications in genes, destroying the effectiveness of the treatment, one famous example being of Jesse Gelsinger who was the first person to die after receiving gene therapy.

Nevertheless, gene therapy has come a long way and its methods have improved immensely. The advantages of gene therapy are greater than its disadvantages because of its ability to cure diseases “incurable” by conventional methods.

Due to these reasons gene therapy has given people another chance at living, especially those with hereditary diseases.

Gene therapy has the potential to eliminate and prevent these genetic defects such as cancer, cystic fibrosis, sickle cell anemia and certain forms of dementia and even diseases like AIDS and cancer.

In whatever way, gene therapy will become a common way to treat diseases in the 21st century. In recent years, researchers have been able to successfully treat patients suffering from hemophilia by inserting a gene that improved their ability to form blood clots.

Additionally, China recently announced that it had enrolled lung cancer patients for gene therapy using CRISPR technology, and in some cases viral vectors were used to treat inherited blindness.

Gene therapy will see more advancements and refinements in the future. On such example is the ability to treat muscular dystrophies and lysosomal disorders. The developments will allow to overcome immune suppression to prevent an immune response which has been shown to cause death. Moreover, future vectors may be different than viral vectors and may include microRNA regulated expression.