The Deerwalk team is full of computer engineers and genomic scientists dedicated to solving human problems. Crazy things happen when our genomics and engineering teams meet. This month, we’re here to describe gene therapy and, naturally, we liken the human body to a computer to start our description.
The human body is like a computer. Computers are full of different types of code that is executed to deliver the programs we use every day. The computer maintains an environment that allows us to connect to Wi-Fi, surf the web and write a document. Similarly, the human body is full of DNA, which is a set of codes that define how a particular human or any particular organism functions. The body also maintains an environment that allows us to move, learn and think about cool analogies.
Did you get the flu this season or the latest computer virus? In ideal conditions, both the computer and human body function optimally. But people get sick from bacteria, viruses, worms etc. and computers are attacked by viruses. When we get sick, we take medicine and, when our computers get a virus, we download software that fixes it.
One of our team members found a memory leak this week; not in his body, of course. It was in one of the computer programs. Sometimes the programmers overlook something and a small glitch turns into a big problem. This is a lot like cancer where a change in the genetic code causes a mutation of how the body functions. The remedy is to correct the faulty code. The engineers submitted a bug fix and immediately stopped the memory leak. Gene therapy is like the bug fix process where we use medicines that specifically address genetic code variants to help people get better. Gene therapy allows us to search through an enormous number of genetic codes and replace faulty DNA with correct DNA.
Our experts analyze gene sequences for known variants and work with physicians to appropriately identify the best cure. We’re excited about the field and expect that individualized care, like gene therapy, will positively improve human health.
Now for the technical bit. Direct and cell based (indirect) gene therapy are the two methods to improve patient health. In the direct method, the gene is packaged inside a specially engineered virus that goes into the cell and replaces the variant. Retrovirus is the most commonly used virus to do this. Once inside the patient, the engineered virus enters the cells and replicates. The natural replication process changes the patient’s DNA. The indirect method is the same as the direct method except it’s done in a laboratory instead of directly inside the patient. The result is a group of therapeutic cells that can return to the patient and help their health improve.
Gene therapy can be classified into somatic and germline depending on the type of cells used. Non-reproductive (or somatic cells) from the patient are used in somatic gene therapy. These cells only work on the patient and do not transfer to their offspring. This is more practical while treating individual disease. Germline gene therapy focuses on improving the health of offspring and uses sperm or egg reproductive cells. This modification in the gene is now transferrable to the later generations.
The first approved experimental gene therapy in the United States happened in 1990 and focused on the genetic disease Adenosine Deaminase-deficiency Severe Combined Immunodeficiency (ADA-SCID). ADA-SCID is a severe immune system deficiency. The successful treatment was performed on a four year old girl named Ashanti DeSilva, suffering from ADA-SCID. Unfortunately, the treatment was only temporary, but clinical trials have been performed for several genetic diseases including thalassaemia, immunodeficiencies, haemophilia and cystic fibrosis.
Like our computer bug fix, the treatment by this method looks easy. It seems as though we could just cut off the defective portion and replace it with the normal genes. The prospect for such treatment looks bright. However, there are obstacles that are hindering its progress. The foremost problem is the patient’s immune response. Like the antivirus software, our immune system attacks any foreign particle or virus. The patients are blocking some of the engineered viruses as well. Another problem is specificity. Scientists haven’t been able to become 100% certain that the therapeutic gene will be inserted in the desired location and only in the desired location.
Fortunately, we have the best minds in the world working on this. Research is performed at major academic centers around the world and we’re actively following the work being done. Gendicine and Glybera are two drugs already approved by China and the European Commission respectively. Experiments and clinical trials are ongoing to cure seemingly uncureable diseases. It will definitely take time. We’re hopeful that individualized medicine, like gene therapy, will become as common as aspirin in near future.