Human Gene Therapy & antisense therapy


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Introduction to gene therapy : 

Introduction to gene therapy Gene therapy is “the use of genes as medicine”. Gene therapy is the process of inserting of genes into cells to treat diseases. The gene used to a genetic disease is called gene medicine or remedial DNA. It involves the transfer of a therapeutic or correct gene into specific cells of an individual in order to repair a faulty gene. The gene medicine is introduced into germ cells such as egg, sperm, and zygote or somatic cells such as liver, skin and bone marrow cells. The gene medicine may replace the function of the defective gene or block the activity of the defective gene to cure the diseases.


BACKGROUND: On September 14, 1990 at the U.S. National Institutes of Health W. French Anderson, M.D., and his colleagues performed the first approved gene therapy procedure on four-year old Ashanthi DeSilva. Born with a rare genetic disease called severe combined immunodeficiency (SCID), she lacked a healthy immune system, and was vulnerable to every passing germ. Children with this illness usually develop overwhelming infections and rarely survive to adulthoodm or infection.

Two Strategies : 

Two Strategies In Gene Augmentation Therapy:- A DNA is inserted into the genome to replace the missing gene product. This is appropriate for the treatment of inherited disorders caused by the loss of a functional gene product. In case of Gene Inhibition Therapy:- The antisense gene inhibits the expression of the dominant gene (pathogenic gene) or interferes with the activity of the product. This is suitable for the treatment of infectious diseases, cancer and inherited disorders caused by inappropriate gene activity.

Approaches for Gene Therapy : 

Approaches for Gene Therapy A. Somatic Cell Gene Therapy:- The non-reproductive (non-sex) cells of an organism are referred to as somatic cells. E.g., Bone marrow cells, blood cells, skin cells, intestinal cells. It involves the insertion of a fully functional and expressible gene into a target somatic cell to correct a genetic disease permanently. B. Germ Cell Gene Therapy:- The reproductive cells of an organism constitute germ cell line. Gene therapy involving the introduction of DNA into germ cells is passed onto the successive generations.

Types of Gene Therapy : 

Types of Gene Therapy Ex-vivo therapy In vivo therapy Anti-sense therapy. Embryo therapy.

1. Ex Vivo Gene Therapy / transplantation or tissue grafting : 

1. Ex Vivo Gene Therapy / transplantation or tissue grafting In this method, some cells are taken from an appropriate organ of patient, remedial gene is introduced into the cells, and then transplanted back into that organ. Examples : Bone marrow transplantation Liver transplantation Kidney transplantation

Steps involved in the ex vivo gene therapy: : 

Steps involved in the ex vivo gene therapy: Isolate cells with genetic defect from a patient. Grow the cells in the culture. Introduce the therapeutic gene to correct gene defect. Select the genetically corrected cells (stable transformants) and grow. Transplant the modified cells to the patient.

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A man with a Genetic defect Isolated cells In vitro culture Genetically Transformed Cells defected Transplantation Gene medicine Fig: The procedure for ex –vivo gene therapy

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Fig: General map of a typical retrovirus 5’-LTR ψ gag pol env 3’-LTR 5’-LTR ψ x P 3’-LTR Fig: Gene map of a modified retrovirus for use in gene therapy X = Therapeutic gene, P = Promoter gene

Examples of ex vivo gene therapy:- : 

Examples of ex vivo gene therapy:- Therapy for Adenosine Deaminase Deficiency. Therapy for Lesch-Nyhan syndrome. Therapy for Hemophilia.


TREATMENT OF ADA DEFICINCY PATIENT BY BONE MARROW TRANSPLANTION Bone marrow is a soft tissue in the medullary cavities of bones. Immuno-deficiency diseases are mainly concerned with the derivatives of marrow cells. Eg. Severe combined immunodeficiency (SCID). Is a genetic disease in man due to mutation in adenosine deaminase gene. Adenosine and deoxyadenosine get accumulated in the blood, these substance are toxic to B-cells and T-cells. The sufferer dies within 3 years after birth.

Therapy for Adenosine Deaminase Deficiency : 

Therapy for Adenosine Deaminase Deficiency

Viruses : 

Viruses Retroviral Vector System:- A plasmid in association with a retrovirus, a therapeutic gene and a promoter is referred as plasmovirus. The plasmovirus is capable of carrying a DNA (therapeutic gene) of size less than 3.4kb.

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Adenoviruses (with a DNA genome) can infect most of the non-dividing human cells. This vector system based gene therapy requires periodic administration of recombinant viruses. The efficiency of gene delivery by it can be enhanced by developing a virus that can specifically infect target cells. This is possible by incorporating a DNA encoding a cell receptor protein. Adenoviral Vector System:-

Gene Therapy Strategies for Cancer : 

Gene Therapy Strategies for Cancer Gene therapy is the latest and a new approach for cancer treatment. Chemotherapy for cancer patients often kills healthy cells as well as cancer cells. In an ex vivo trial, bone marrow stem cells from women with ovarian cancer were infected with a virus carrying a gene to make them more tolerant to chemotherapy.

3. Anti-Sense Therapy : 

3. Anti-Sense Therapy Anti-sense therapy is a form of treatment for genetic disorders or infections. The treatment of genetic diseases by introducing a remedial gene that prevents the expression of the specific defective gene is called antisense gene therapy. The defective gene in the patients cells produces mRNA by transcription. The mRNA gets translated into a defective protein. Accumulation of this protein results in a genetic disease.

Principle : 


Applications : 

Applications In cancer therapy In hypertension In AIDS

Anti-Sense Therapy for Cancer: : 

Anti-Sense Therapy for Cancer: Oncogenes are the genes responsible for the causation of cancer. The dominantly acting oncogenes can be targeted in antisense technology by using antisense oligonucleotides. Antisense RNA molecules are more frequently used in cancer therapy

Anti-Sense Therapy for Hypertension : 

Anti-Sense Therapy for Hypertension


REFERENCES S.P.Vyas & V.K. Dixit “Pharmaceutical Biotechnology” CBS Publishers & distributors, first edition; page no. 402-405. 2. V. Kumaresen “Biotechnology” Saras publication, first edition page; no. 479-489. 3. Biotechnology by Dr U. Satyanarayana (professor of Biochemistry) first edition; page no: 169. 4. Pharmaceutical Biotechnology Edited by Daan JA Crommelin and Robert D Sidearm. Page no:350-351. 5. 6.

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