Contact:
sales@biotechnologyforums.com to feature here

Thread Rating:
  • 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Overview of Gene Therapy and its implications in medical field
#1
The progress in the field of Recombinant DNA technology (RDT) has initiated the discovery of new medicines and therapeutics for various diseases. It has also helped in the diagnosis and detection of different infections, genetic diseases and Cancer. The nucleic acid-based biopharmaceuticals, which includes gene therapy and antisense therapy, have great potential to create a revolution in the field of medical science. However, their role in the medical field can materialise completely only after solving the different difficulties encountered in their successful implication.

Gene therapy can be utilized for the correction of different genetic diseases resulting due to the presence of a defective gene, which arises due to mutation or is inborn. The therapy works on the principle of the introduction of the stable gene, to correct the faulty gene expression or provide protective function, into the genetic complement of the cell with the use of different vectors useful for the purpose. The detailed understanding about the different molecular mechanisms related to the diseases within the body helps in the successful application of the gene therapy in combating the diseases. Due to the adaptation of the human body through evolution to resist the entry of foreign genetic material within its genome has posed a problem for the use of gene therapy. However, the use of viruses as vectors for the introduction of genes into the body has helped in overcoming the problem largely due to the ability of the viruses to overcome the barriers and incorporate their genetic material into the genome of the human cells.

There are three categories of somatic gene therapy:
i) ex-vivo, in which the cells removed from the body are incubated with vectors and then the modified, genetically engineered cells are re-introduced into the body. However, this procedure is restricted with blood cells, which can be removed from and re-introduced into the body.

ii) In-situ, in which the introduction of the vector carrying the gene is done into the affected tissues. This procedure is useful in the treatment of muscular dystrophy, which involves the introduction of the vector carrying the gene of dystrophin into the muscle and the treatment of cystic fibrosis, involving the introduction of the vector expressing the gene of cytokine or toxin into the tumor-infected muscle.

iii) In-vivo, in which the vectors carrying genes are introduced directly into the blood stream of the infected individual. This process has not been applied clinically yet, however to apply gene therapy for therapeutics, the development of in-vivo introduction of injectable vectors is essential.


For gene therapy, two types of vectors have been studied: RNA virus vectors and DNA virus vectors. The Retroviruses were initially chosen as the best vehicle for gene transfer due to a number of advantages they provided such as efficient gene transfer with stable integration into the host cell genome, providing the possibility of long-term expression. As they have evolved into non-pathogenic parasites, hence have minimal risk in their usage. These vectors are replication-defective due to the removal of all their viral genes. However, there are some problems faced by these vectors such as for obtaining proper efficient delivery into the target cells, transduction of the non-dividing cells, sustainment of long-term gene expression, and the development of a cost-effective method of manufacturing the viral vector. DNA viruses, which have been most often used for gene transfer are Adeno virus, Adeno associated virus (AAV), herpes simplex virus, etc. The immune response of the cells against the viruses, which affect the integration into the host genome as also the non-specific integration of the gene are some of the problems faced by the DNA virus vectors. Hence, to solve the problem of generation of immune response, non-viral vectors like liposomes and polypeptides are being developed, although their low transduction efficiency poses the biggest disadvantage of their use.

Thus, it can be said that although gene therapy has potential to be developed as therapeutics for a number of genetic diseases, however the application has some major limitations, due to which it has not found practical application, like:

i)the complexity of the genetic diseases affecting a number of cells and tissues at the same time and the molecular mechanisms involved with the development of the disease,

ii)the insufficiency in the level of gene expression and its regulation,

iii)improper identification of the actual genes responsible for a particular disease, and

iv)the insufficiency of the patient population to be studied for various diseases and for conducting clinical trials.

Hence, although gene therapy is making a very slow progress in being used as a form of treatment, it shows great promise and in future, the modification in the vectors used and the development of better strategies for the purpose will help in the practical application of gene therapy in therapeutics.
Like Post Reply
#2
What are the main obstacles of gene therapy?

Idea that genes could be used for therapeutic purposes is old; term in coined back in 1972. FDA approved first gene therapy experiment in humans in 1990. However, even with all the promises this therapeutic approach may have – it doesn’t evolve as quickly as we might hope.

It all started with experiment on 4 year old girl suffering from the adenosine deaminase deficiency and severe combined immunodeficiency disease (ADA SCID). This is extreme type of immune system disorder where both T and B cell lymphocytes fail to develop properly and as a result body can’t fight even the slightest infection. Usual treatment for ADA SCID is bone marrow transplantation and it needs to match perfectly (must be donated by the close relative). Mutated gene responsible for sickness is located on the X chromosome (IL2RG). In the mentioned experiment, T cells were extracted from her blood, normal copy of the ADA gene was inserted in the T cells, and they were brought back to the body. Result was normalization in the T cell number, but girl had to continue receiving gene therapy to ensure appropriate working of the immune system in the future. This experiment showed that gene therapy could be a possible solution for the severe disorders. With the initial success, gene therapy using viral vectors carrying healthy gene start applying to a bigger number of patients, but it was soon discovered that viral vector used in the study could induce expression of some other genes beside expected one. Insertion of corrected gene triggered a nearby oncogene resulting in leukemia in a lot of patients. Before discontinuation due to serious side effect, this therapy managed to restore immune system in 17 children.

Besides having questionable viral carriers that might trigger other than expected genes, few other problems exists as well. Virus can target wrong cell. If used to treat cancer and skip invading the right cell or appropriate DNA place, it can produce even more damage by accelerating tumor growth, for example. Sometimes, even if right cell and part of DNA is targeted – gene expression could fail or it can produce unexpected effect. Virus used for cystic fibrosis treatment produced immune response even when inserted in the right place. Also, cells need to divide frequently so the viral vector could insert and express gene efficiently. Bone marrow cells are not undergoing as much cell divisions as needed and as a result they can’t be genetically altered always.

There are also some ethical issues associated with gene therapy. Not all genetic diseases are obvious. If you decide to test yourself, you may discover disorders that could place you in a high risk group that will inevitably affect all aspects of your life - from employment to the health insurance. With people planning a family, option to test your future offspring may result in increased abortion rate since genetic testing could show abnormalities that normally wouldn’t be seen. But it might help parents that are familiar with their altered genetic status to prevent having children with the same genetic disorders. Other than that, what genetic abnormality would be considered important and worth of healing? Which one would have higher priority? Like genes responsible for diseases, other could be responsible for good looking (beauty), and genetic therapy could easily become a tool in cosmetic industry and skip research in the field where is more important.

There are a lot of challenges gene therapy needs to overcome. Most illnesses could not be eradicated easily and long lasting treatments are inevitable part of the gene therapy. Immune system is responding any time vector is inserted. Viral vectors are not always precise in targeting certain cells or part of DNA. Some disorders are result of multiple dysfunctional genes and it’s hard to design a vector that could improve all of them. Vectors could result in disease aggravation or oncogenesis if not inserted properly.

It may sound that negative aspects are dominating, but for the past 5 years gene therapy showed increased success in healing Leber's congenital amaurosis, adrenoleukodystrophy, chronic myelogenous leukemia and Parkinson's disease. It needs to be improved, but with modern techniques it’s just a matter of time.
Like Post Reply
  

Possibly Related Threads…
Thread
Author
  /  
Last Post
Replies: 0
Views: 7,319
05-23-2017, 05:48 PM
Last PostN0tail
Replies: 0
Views: 7,350
04-17-2017, 10:07 PM
Last Postpriyansha sinha
Replies: 3
Views: 28,152
02-03-2017, 01:10 AM
Last Postsanjeev Harnandan
Replies: 3
Views: 33,244
03-12-2015, 05:39 PM
Last PostPatel12



Users browsing this thread:
1 Guest(s)

Overview of Gene Therapy and its implications in medical field00