Gene therapy

Gene therapy is a technique that modifies a person's genes to treat or cure disease.

1. Gene Therapy Current progress and Future prospects

2. Gene Therapy G ene therapy Is the insertion of genes into an individual’s cells and tissue to treat a disease H as been studied as a potential treatment for genetic disease. A vector must be used to deliver the therapeutic gene to the target cell. A functioning copy of the gene is packaged into a vector. M odified virus acts as a transport vehicle for functioning gene.

3. Gene Therapy Study purpose of gene therapy This is treatment for many disease. For example, Cancers Blood disease Central nervous system disease Immune system disease Cardiovascular disease Muscular dystrophy Huntington’disease

4. Gene Therapy Types There are two types of gene therapy. Somatic cell gene therapy Germ line gene therapy

5. Gene Therapy

6. Gene Therapy

7. History

8. Gene Therapy

9. Gene Therapy Progression 90s The first approved gene therapy clinical research in the US took place on 14 September 1990. Four-year-old Ashanti DeSilva received treatment for a genetic defect. The effects were successful, but temporary. Fig: Ashanti DeSilva

10. Gene Therapy Progression 90s Cancer gene therapy was introduced in 1992/93. The beginning of cancer immunogene therapy. Effective due to the anti-tumor mechanism of IGF-I antisense.

11. Gene Therapy Progression 2000s The modified cancer gene therapy strategy of antisense IGF-I RNA H as shown promising results in the treatment of six different malignant tumors. They are, G lioblastoma , C ancers of liver, C olon , Prostate , Uterus , Ovary,

12. Gene Therapy Progression 2000s R epaired errors in messenger RNA derived from defective genes has the potential to treat thalassaemia , cystic fibrosis and some cancers . (2002) Gendicine delivers the tumor suppressor gene p53 using an engineered adenovirus for the treatment of head and neck squamous cell carcinoma. Fig: Head and neck cancer

13. Gene Therapy Progression 2000s Successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells . (2006) S uccessful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system . (2006)

14. Gene Therapy Progression 2000s U se of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope(2006) R esearchers announced the first gene therapy trial for inherited retinal disease . (2007)

15. Gene Therapy Progression 2010s An 18-year-old male patient in France with beta-thalassemia had been successfully treated in 2010. Human HGF plasmid DNA therapy of cardiomyocytes is a potential treatment for coronary artery disease and myocardial infarction. (2011) The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in 2012.

16. Gene Therapy Progression 2010s 10 of 13 patients with multiple myeloma were in remission or very close to it three months after being injected with a treatment involving genetically engineered T cells (2012). Three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells (2013)

17. Gene Therapy Progression (2010s) T wo children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery . (2013) Fig: Alysia Padilla- Vacarro and daughter Evangelina on the day of her gene therapy treatment

18. Gene Therapy Progression (2010s) S ix choroideremia patients had been treated with adeno -associated virus with a copy of REP1 . (2014) Clinical trials of gene therapy for sickle cell disease were started in 2014.

19. Gene Therapy Progression (2010s) A baby girl Layla Richards treated with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. (2015) A trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. (2016) Fig: Layla Richards

20. Gene Therapy Progression (2010s) T he FDA approved tisagenlecleucel for acute lymphoblastic leukemia . (2017) This is the first form of gene therapy to be approved in the United States . Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. (2017)

21. Gene Therapy Progression (2010s) T he FDA approved Luxturna , the first in vivo gene therapy, for the treatment of blindness due to Leber's congenital amaurosis . Spark Therapeutics has been rewarded with an FDA approval for their Luxturna therapy . (2018) Clinical trials by Sangamo involving gene editing using Zinc Finger Nuclease (ZFN) are ongoing . (2019)

22. Future of G ene Therapy The FDA approved the first gene therapy in 2017, marking a significant moment in the history of health care. CRISPR/Cas9 gene-editing technology offer better and more effective gene therapies for various conditions It is now being evaluated as a treatment for multiple cancers, HIV, and other potentially life-threatening conditions . The number of companies pursuing gene therapies has rapidly increased.

23. Future of Gene Therapy G ene therapies in development ADA-SCID Alpha-1 antitrypsin (A1AT) deficiency β- thalassemia (severe sickle cell ) Cerebral adrenoleukodystrophy (CALD ) Choroideremia Cystic Fibrosis Glaucoma Wiskott Aldrich syndrome (WAS) Hemophilia A Hemophilia B IRD (vision loss ) Metachromatic leukodystrophy MPS I (Hurler syndrome ) MPS II (Hunter’s syndrome ) Pompe Disease Spinal Muscular Atrophy (SMA ) X-linked myotubular myopathy

24. Future of Gene Therapy Human clinical trials based on gene editing technology (updated 2019 ) Cancer (PD-1 knockout ) Hemoglobinopathies ( β- thalassemia, sickle cell disease ) Hemophilia B HIV MPS I (Hurler syndrome ) MPS II (Hunter’s syndrome ) All of the trials above involve somatic cell gene editing in humans.

25. Limitation of Gene Therapy Lack of knowledge about the disease at the DNA level Multiple gene effects cannot be treated today Affected tissue must be accessible to gene therapy In case of dominant disorder, homologous rearrangement has to occur for successful replacement of defective gene.

26. Limitation of Gene Therapy Retroviral contamination and spread in the body. High technical expertise required. Many ethical questions to be answer properly. Gene therapies priced between 1 and 3 million dollars. Spark is selling Luxturna for 425K per eye, so 850K for both eyes.

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