Genetic therapy

Gene therapy in a broader sense, any therapeutic procedure in which the action of manipulating genes, and the goal is to replace damaged or replaced absent copy of the gene, the normal functional copy. In many gene therapy include therapies that are already present in medicine for decades. This is an example of this kind of therapy that affects cells of the immune system by altering the expression of certain genes in them. However, today the gene therapy begins to be used in tumor therapy by introducing gene killer or the vaccination by introducing a gene encoding a potent immunogen. 

However, the concept of gene therapy is restricted to processes in which the genetic material of the cell entries. 

Most often they were used viral vectors based on adenoviruses, retroviruses, lentiviruses, adeno-associated viruses and herpes simplex viruses. 

· Retroviruses: Most protocols for gene transfer used retroviral vectors. For use in oncology, the ability of retroviruses to integrate into dividing cells, it is shown as an advantage. Attempts to transfer ex vivo proved to be very successful. However, there are several disadvantages. Retroviruses have a small gene capacity of only eight kilobases. Serum complement can be inactivated. Currently achieved titer was low compared to that which would be achieved in the treatment of large tumors. The patient may receive a Limited conical retroviruses. 

· Adenoviruses: Limitations when working with retroviruses imposed by the need to find other vectors that would be more satisfactorily used in gene therapy. Attention is focused on adenoviruses, when it was revealed to possess double-stranded DNA and efficiently as possible transduction in different cell types regardless of the stage of mitotic cells. These vectors can be produced in higher titers of retroviruses. Studies have shown that the minimum amount of virus can achieve a sufficient level of expression in most tissues, except in the haematopoietic cells. Use of the adenoviral vector is first tested in the treatment of noncancerous disorders such as cystic fibrosis, but it is also used in treating the cancer. Investigating, for example, the possibility of their use when installing gene of HSV-tk in patients with tumors of the brain and liver, and the tumor-supresijskog p53 gene in patients with tumors of the lung, head and neck. Although adenoviruses showed good properties for use in gene therapy, even they are not without drawbacks. The presence of unmodified viral genes in the recombinant virus can cause an immune response to these antigens, and thus the cells against the wearer. He has investigated a number of viruses with unique properties useful for applications in gene therapy. Some of them are the herpes simplex virus, Avipox virus, Vaccinia virus and Baculovirus. 

One of the areas of research, the most promising research nevirusnih vectors. They allow the transfer of therapeutic genes into cells without the help of viruses. Four such primarily include liposomes, molecular conjugates and "naked" DNA. The liposomes were combined with the DNA of any size and form of the lipid-DNA complex, which can be entered in different cell types. This system, however, does not have a tissue specificity and therapeutic effectiveness in its use is not yet satisfactory. Due to the need for greater specificity for certain types of cells, to the conjugate molecule is produced as proteins or synthetic molecules with the capacity of binding to cellular DNA or RNA, which is linked from the desired gene, so that a protein-DNA complex. Producing conjugate increases the desired specificity for certain cells, and the lack of this system is too short life conjugates. Application of "naked" DNA is the simplest way of its incorporation into the target cell without the use of viral vectors or nevirusnih. The cells are infused by mechanical methods such as direct injection into the tissue or tissues of a high speed bombardment with DNA bound to the gold particles. This method is a method hitherto been tried in transgenskoj immunotherapy in the treatment of colon carcinoma and melanoma. The disadvantage of this method is also the lack of tissue specificity and the need for surgical approach to the tumor tissue if it is not located in an accessible place. 

Gene therapy will not replace conventional forms of treatment of malignant tumors, but will, in combination with conventional treatment, surely improve their achievements and more importantly, will have their application in suppressing residual (residual) disease, which ranks high second place in the ranking of causes of death in humans. 

Most often they were used viral vectors based on adenoviruses, retroviruses, lentiviruses, adeno-associated viruses and herpes simplex viruses. 

The most important property by which distinguish viral vectors is the efficiency of gene introduction into the cellular genome, and the length and stability of expression of the gene. Various viral vectors are distinguished by size and "burden" that can be entered into the cell, ie. Length of the DNA by using them we can insert into the cellular genome. You also differ in whether infect dividing cells, those that are suspended or both. Some viral vectors possess particular tissue specificity, for example. HSV (herpes simplex virus) which is used for insertion of genes into nerve cells. 

However, this approach is not without risk, because the immune system of patients may react to the introduction of the virus, and the virus completely eliminated, sometimes with potentially fatal immune reaction. There is also concern, so far unconfirmed, that the viral genome integration into the host cell genome could disrupt the regulation of its growth and multiplication, and lead to malignancies. 

Successful gene therapy must not be toxic, must be specific to particular cells with significant gene expression without immune response. There are still problems in the construction of the viral vector was neviralnog or to assist in correcting genetic defects, but many studies are focused on the concept of treating a functional gene in malignant, polygenic and monogenic disorders such as Duchenne's muscular dystrophy. 

Life is a risk, and genetics will help to facilitate risk control. The physician-geneticist must have knowledge "up to date" in order to assess the psychological and social risk related to genetic information. Hope is all researchers that the new techniques make it possible to test all genes for each person. The meaning of the term "disease" will be changed, and predisposing condition will be an indication for genetic therapy.