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GENE THERAPY is it the feature?

Date: Tue-Jan-26-2016-
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As I said in the introduction, gene therapy was once considered as a fantasy.It is the most wonderful application of recombinant DNA technology.The first breakthrough in gene therapy came when a girl who was suffering from Severe Combined Immunodeficiency was treated with gene therapy.Here the patient had deficiency of Adenosine Deaminase enzyme and it was treated by transferring the normal gene for adenosine deaminase.In gene therapy the genes are delivered into a cell to generate a therapeutic effect by correcting the existing abnormality.Here the abnormal gene may or may not  be replaced, but the healthy gene is introduced.Currently only somatic gene therapy is done, and germ cell gene therapy is considered as unethical.

 

Procedure of Gene Therapy

 



 

Just as we discussed in recombinant DNA technology, its all about isolating a healthy gene with all the parts needed for expression, then incorporation the gene into a carrier or vector and finally deliver the vector to the target cell.There are three ways by which gene can be introduced.First method is called Ex Vivo strategy where the cells of patients are cultured in laboratory, new genes are introduced into that cells and theserna, modified cells are introduced back into the patient.The second method is just opposite to this where the vector is administered directly to the cell.It is called In Vivo strategy.One example where this method is used is in cystic fibrosis where the vector is introduced into respiratory tract cells.The third method is called In situ strategy where expression vector is injected to the patients either intravenously or directly to the tissue.Once the normal gene reaches the cell, it get incorporated in DNA or work along with the DNA producing the deficient substance in body.Thus normal condition can be attained and disease can be cured.

 

The vectors mainly used for this purpose are Retroviruses, Adenoviruses, adeno associated virus particles, and herpex simplex viruses.Non-virus system include liposomes plasmids and physical methods.Retrovirus are actually RNA virus that replicate through DNA intermediate and they will have enzyme called reverse transcriptase.Moloney Murine Leukemia Virus (MMLV) is commonly used.What is done with retro virus is that, the disease causing and replicating part of the RNA will be replaced by the normal gene we want to get introduced.The virus protein covering also will be fixed to the virus in other means.Its a total genetic engineered product.This replication deficient ineffective virus is then introduced into the cells of patient.Inside the cell, this virus will produce the DNA copy of the gene and just like it infect the host DNA it will introduce the gene into the host DNA.Here in actually case the virus DNA was to be introduced, but since we have replaced it by genetic engineering, now the desired DNA is getting introduced.Thus the gene start working in the host DNA and the disease is cured.The main advantage of this method is that, since the virus is engineered, its very safe and also this virus can infect many types of cell.This method is best when we consider disease produced by single gene mutations.But the main disadvantage is that only dividing cells can be the targets of retrovirus and also less amount of virus can be produced in this way.There is also a theoretical chance that the virus again be infectious by mutating back to the original form.

 

One of the other system used for the same purpose is Adeno virus.The main difference is that adeno virus are DNA virus.When the virus with the human gene reach the nucleus of the cell, it wont integrate the gene into the host DNA but will remain as epichromosomal particle.It will be separate from the host DNA and it will express the gene.The main advantage is that it can be made in large numbers and it will easily infect a host cell.But the expression will be for a very little time, maybe weeks or months.There is still another system for carrying gene which is called Plasmid Liposome complex.It is a non-viral vector system.Liposomes are artificial lipid bi layer and form  complex with plasmid carrying normal human DNA.Because the complex is lipid, it can easily pass the plasma membrane and positive charge in the complex will spontaneously attach to negative charge DNA.The main advantage is that large genes can be transferred and it wont replicate or evoke any immune response.But there is a disadvantage that most of these complex can get destroyed in host cell and thus majority of cases can be unsuccessful.So if this is not the method preferred ,then a different form of non-viral gene transfer can be considered which is called as Gene gun.As the name implies, it  is a particle gun and plasmid DNA coated with tungsten particles are literally shot into the cell using helium pressure discharge.This help the particles to reach the target tissue and its very fast and can be done in most cells.But cellular damage and transient gene expression are the drawbacks.In general, though gene therapy can be used to treat many disease,at the same time it has got many limitations like inconsistent result, lack of ideal vector, sometimes death during the course of gene therapy due to some enzyme deficiency, reactivation of retro virus leading to leukemia etc.It will take many more years before gene therapy is fully successful

 

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So with recombinant DNA technology, a new revolution has come in the medical field.With gene therapy the days are not far when there is cure to every genetic disease.Presently gene therapy is most effective in treating inherited disorders caused by single gene.It will take decades before gene therapy can be used as a common clinical procedure.But day by day the application of recombinant DNA technology are increasing and we already enjoy many of its fruit.
[d] By: fetter
Date: Tue-Jan-26-2016
Response
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