Genetics & Human Diseases • About 4,000 human diseases are thought to be inherited. • Scientists are making good progress figuring out where genes are located on chromosomes. • Genetic diseases are caused by mutations, or incorrect sequences, in the normal form of the gene.
What is Gene Therapy? • Gene therapy is a treatment or cure for disorders caused by mutated genes. • It involves adding a normally functioning copy of the gene(s) to enough affected cells to restore normal function.
What is Gene Therapy • Germline gene therapy would be the permanent transfer of a gene into sperm or egg cells. • Future generations would be “cured”. • Somatic cell (body cell) gene therapy is transfer of a section of DNA to any cell of the body that doesn’t produce sperm or eggs. • - Effects of gene therapy will not be passed onto the patient’s children
Gene Therapy Successes • Although no gene therapies have been approved by the FDA for sale, some diseases have been experimentally successful: • Melanoma (skin cancer) • Severe Combined Immunodeficiencies • Hereditary Blindness • Sickle Cell Anemia
Adenoside Deaminase (ADA) Deficiency ADA-deficient persons are affected by severe immunodeficiency, with recurrent infections that might be life-threatening. First disease approved for gene therapy. Autosomal recessive disorder. The drug exists but is very expensive, needs to be injected in vein for life.
Video “bubble boy” https://www.youtube.com/watch?v=-G_SW8LmidA Gene therapy cure bubble baby https://www.youtube.com/watch?v=lSz1ZINMwj8
How is it done? Viral Vector Carrying Healthy Gene Cell with mutated gene(s) Vector inserts healthy gene into cell New gene in the cell along with original genes Functional proteins are created from the therapeutic gene causing the cell to return to a normal state.
Gene Therapy To design and carry out a gene therapy treatment, a researcher must: • Identify the gene(s) responsible for the disorder. • Make copies of the normal gene. • Insert the copies into vectors. • “Infect” the affected cells with the vectors. • Activate the gene so that transcription and translation take place.
Viruses as Vectors • Replicate by inserting their DNA into a host cell • Gene therapy can use this to insert genes that encode for a desired protein to create the desired trait • Four different types • Adenovirus • Adeno-Associated Virus (AAV) • Retrovirus • Herpes Simplex Virus (HSV)
Viruses • Adenoviruses: Common causes of respiratory illness • Adeno-Associated Virus: Is not currently known to cause disease, but can cause a milld immune response • Retrovirus: Any of a group of RNA viruses that insert a DNA copy of their genome into the host cell in order to replicate e.g. HIV • Herpes simplex virus: cause watery blisters in the skin or mucous membranes of the mouth, lips, nose or genitals
Vector Advantages and Disadvantages • Adenovirus • Infects many cell types • Does not integrate into host genome and can be lost. • Adeno-Associated Virus (AAV) • Integrates into host genome and cannot be lost • Difficult to work with. • Retrovirus • Integrates into host genome and cannot be lost • Integrates into host genome and can cause cancer • Herpes Simplex Virus (HSV) • DNA stays in nucleus without integrating into host genome. • Only infects cells of the nervous system.
Gene therapy techniques • Gene augmentation therapy • This is used to treat diseases caused by a mutation that stops a gene from producing a functioning product, such as a protein • This therapy adds DNA containing a functional version of the lost gene back into the cell • It is only successful if the effects of the disease are reversible or have not resulted in lasting damage to the body
Gene therapy techniques • Gene inhibition therapy • Suitable for the treatment of infectious diseases, cancer and inherited disease caused by inappropriate gene activity • The aim is to introduce a gene whose product either: • Inhibits the expression of another gene • Interferes with the activity of the product of another gene
Gene therapy techniques • Killing of specific cells • Suitable for diseases such as cancer that can be destroying certain groups of cells • This can be achieved in one of two ways: • The insert DNA contains a “suicide” gene that produces a highly toxic product which kills the diseased cell • The inserted DNA causes expression of a protein that marks the cell so that the diseased cells are attacked by the body’s natural immune system
Challenges of gene therapy • Delivering the gene to the right place and switching it on: • Delivering a gene into the wrong cell would be inefficient and could also cause health problems • Even once the right cell has been targeted, the gene has to be turned on • Cell sometimes obstruct this process by shutting down genes that are showing unusual activity
Challenges of gene therapy • Avoiding the immune response: • This is usually done by using vectors that are less likely to trigger an immune response • Making sure the new gene doesn’t disrupt the function of other genes • The cost of gene therapy