1. GENE THERAPY Presented to : Dr.Leslye Jhonson Presented by: Khazeema Yousaf & Maheen Alam Biot 412: Medical Biotechnology

2. What is gene therapy? How does gene therapy works? Tools of Trade—Vector What are the types of gene therapy? Advantages and disadvantages of gene therapy History What is the current status of gene therapy? what factors have kept gene therapy from becoming an effective treatment for genetic disease?

3. Gene therapy is a technique for correcting defective genes responsible for disease development A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common. An abnormal gene could be swapped for a normal gene through homologous recombination. WHAT IS GENE THERAPY?

4. The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered About one in ten people has, or will develop at some later stage, an inherited genetic disorder, and approximately 2,800 specific conditions =one gene

5. HOW DOES GENE THERAPY WORK? For inserting DNA of interest scientists have to have DNA delivery "vehicles" as vectors They can be Viral and non viral-Tools of trade

6. Gene therapy can be exvivo or invivo.

7. TOOLS OF TRADE-VECTORS Non-viral Liposome=Circular piece of dsDNA-plasmid packed into liposome;not specific in targeting Naked DNA=dsDNA,not specific. Effectivness is low but will not activate immune response Viral Retroviruses = create double-stranded DNA copies of their RNA genomes. Then integrated into chromosomes of host Adenoviruses =with double- stranded DNA genomes Adeno-associated viruses = single-stranded DNA viruses, insert their genetic material at a specific site on chromosome 19. Herpes simplex viruses double-stranded DNA viruses that infect a particular cell type, neurons

8. TYPES OF GENE THERAPY

9. advantages of viral vectors:  good at targeting and entering cells.  Some viral vectors might be engineered to target specific types of cells.  modified so that they can't replicate and destroy the cell. drawbacks of viral vectors:  A virus can't "expand" to fit a piece of genetic material larger than it is naturally built to carry.  can cause immune responses, resulting in two potential outcomes: Patients may get sick. A patient's immunity to a virus may prevent him from responding to repeated treatments.

10. HISTORY initiated during the 1960s and early 1970s In 1992 Doctor Claudio Bordignon--- performed the first procedure of gene therapy using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases. This was a world first. genestem cells In 1993 Andrew Gobea born wiith severe combined immunodeficiency (SCID). Blood was removed from Andrew's placenta and umbilical cord immediately after birth, containing stem cells. Retroviruses and stem cells were mixed, after which they entered and inserted the gene into the stem cells' chromosomes.chromosomes In 2003 a University of California research team inserted genes into the brain using liposomes coated in a polymer called polyethylene glycol (PEG). brain

11. In 2006 Scientists at the National Institutes of Health, successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.melanomacancer In May 2006 a team of scientists led by Dr. Luigi Naldin reported a breakthrough for gene therapy in which they developed a way to prevent the immune rejection usimg miRNA On 1 May 2007 Moorfields Eye Hospital and University College London's Institute of Ophthalmology announced the world's first gene therapy trial for inherited retinal disease. In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys using gene therapy, a hopeful precursor to a treatment for color blindness in humanscolor blindness

12. WHAT IS THE CURRENT STATUS OF GENE THERAPY RESEARCH?

13. (FDA) has not yet approved any human gene therapy product for sale. current gene therapy is experimental and has not proven very successful in clinical trial Gene therapy suffered a major setback with the death of 18-year-old jesse gelsinger. Having gene therapy trial for ornithine transcarboxylase deficiency (otcd). he died from multiple organ failures 4 days after treatment.

14. In january 2003, fda placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. In April of 2003 the FDA eased the ban on gene therapy trials using retroviral vectors in blood stem cells. The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy.

15. Presently, gene therapies for the following diseases are being developed: cystic fibrosis (using adenoviral vector), hiv infection (cell-based), malignant melanoma (cell-based), duchenne muscular dystrophy (cell-based), hemophilia b (cell-based), kidney cancer (cell-based), gaucher's disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector).

16. what factors have kept gene therapy from becoming an effective treatment for genetic disease?  Short-lived nature of gene therapy  Immune response  Problems with viral vectors  Multigene disorders

17. Questions??