Genetherapy.pptx Postgraduate pediatric teaching

PG teaching

1. Gene Therapy

2. Objectives Introduction Principles of Gene Therapy Types of gene therapy Vectors for gene therapy Methods of gene therapy applications Gene therapy Conclusions References 2

3. Introduction Gene therapy has the potential to treat diseases that cannot be treated with conventional medicine. It is applied by transferring one or more nucleic acids into a patient’s cells or by modifying a defective gene. The main factors of investment in gene therapy for human diseases include the development of gene therapy vectors, optimization of gene delivery under in vivo and in vitro conditions, and enhancement of the clinical experience. Gene therapy, as an advanced technology, goes beyond the modification of genetic disorders and has spread to a wide range of applications ( Azam et al., 2018). 3

4. Introduction In fact, promising progress made in the treatment of leukemia using modified chimeric antigen receptors (CAR) of T-cells encouraged Science magazine to select cancer immunotherapy as the most important scientific achievement of 2013. Effective approaches to clinical gene therapy include gene delivery to non-dividing cells and tissues (post-mitotic cells) in vivo, or gene delivery to autologous cells out of the body (ex vivo) in which the gene is transferred to the patient through adoptive transfer. Among viral vectors, the adeno-associated viruses (AAVs) have shown the highest clinical success in in vivo gene transfer ( Azam et al., 2018). 4

5. Principles of Gene Therapy 1) Gene modification : Replacement treatment: Replacing a natural gene with a non-natural gene through homologous recombination. Modifier gene therapy: Restoring natural function to a defective gene through selective reverse mutation. 2) Gene transfer method there are 3 physical, chemical, and biological methods for gene transfer. 3) Gene transfer to specific cell line this line is somatic gene therapy and sex cell gene therapy ( Patil et al. , 2012). 5

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7. Types of gene therapy 1) Somatic Gene Therapy : In somatic gene therapy, the somatic cells of a patient are targeted for foreign gene transfer. In this case the effects caused by the foreign gene is restricted to the individual patient only, and not inherited by the patient's offspring or later generations ( Haurigot et al., 2013) 2) Germ Line Gene : Therapy here, the functional genes, which are to be integrated into the genomes, are inserted in the germ cells, i.e., sperm or eggs. Targeting of germ cells makes the therapy heritable ( Wolf et al., 2019). 7

8. Vectors for gene therapy Viral vectors Retroviruses, adenoviruses and adeno-associated viruses (AAV) some commonly used viral vectors whereas some less commonly used viral vectors are derived from the Herpes simplex virus (HSV-1) ( Asad et al., 2017). Non- viral vectors It involves chemical and physical methods such as direct injection of naked plasmid DNA (particle bombardment), receptor-mediated endocytosis and gene transfer through liposomes, polymers, nano particles etc ( Foldvari et al., 2016). 8

9. Adenovirus as a vector in gene therapy Asad et al., 2017 9

10. Methods of gene therapy There are mainly two approaches for the transfer of genes in gene therapy: 1. Transfer of genes into patient cells outside the body (ex vivo gene therapy). 2. Transfer of genes directly to cells inside the body (in vivo) like brain cells ( Cynthia et al., 2018). 10

11. Cynthia et al., 2018 11

12. applications Gene therapy 1-Cancer include glioblastoma, breast cancer, head and neck cancer, non-small cell lung cancer and prostate cancer. 2-Neurological disorders include Parkinson’s disease, Alzheimer’s disease. 3-Inherited diseases include Haemophilia , Cystic fibrosis, “Severe combined immunodeficiencies ” (SCID). 4-Infectious diseases tuberculosis, malaria, HIV and influenza. 5-Cardiac disease ( Ginn et al., 2013). 12

13. Conclusions Gene therapy has made a number of achievements in the last decade. Several significant successes such as treatments now available for diseases such as cystic fibrosis, diabetes, Alzheimer’s disease, Parkinson’s disease, various cancers, etc , can be mentioned. In other words, gene therapy can be applied to a wide range of diseases and includes many methods of gene transfer. Other vector systems are expected to provide further advancement in their clinical applications. Next-generation protocols that will help expand the range of diseases treatable by gene therapy are currently being developed. 13

14. References 1- Yazdani , Azam , et al. "Gene therapy: a new approach in modern medicine." International Journal of Medical Reviews 5.3 (2018): 106-117.‏ 2- Dunbar, Cynthia E., et al. "Gene therapy comes of age." Science 359.6372 (2018).‏ 3- Patil , P. M., et al. "Review article on gene therapy." Research Journal of Pharmacology and Pharmacodynamics 4.2 (2012): 77-83.‏ 4- Ginn , Samantha L., et al. "Gene therapy clinical trials worldwide to 2012–an update." The journal of gene medicine 15.2 (2013): 65-77 .‏ ‏‏‏ 14

15. 5- Asad , Antonela S., et al. "Viral gene therapy for breast cancer: progress and challenges."  Expert opinion on biological therapy  17.8 (2017): 945-959.‏ 6- Foldvari , Marianna, et al. "Non-viral gene therapy: Gains and challenges of non-invasive administration methods."  Journal of Controlled Release  240 (2016): 165-190.‏ 7- Wolf, Don P., Paul A. Mitalipov , and Shoukhrat M. Mitalipov . "Principles of and strategies for germline gene therapy."  Nature medicine  25.6 (2019): 890-897.‏ 8- Haurigot , Virginia, and Fatima Bosch. "Toward a gene therapy for neurological and somatic MPSIIIA."  Rare Diseases  1.1 (2013): 3254-71. ‏ 15

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