10-15-2012, 09:30 PM
(This post was last modified: 10-16-2012, 02:39 AM by Administrator.)
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.
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.
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