Viral Genetics and Gene Therapy Review

Overview of Viral Genetics and Gene Therapy

  • Presenter: Prof. Dr. Saeed Khan, PhD in Microbiology

Understanding Cells

  • Cell Structure: Each human cell contains a nucleus that houses chromosomes.

  • Chromosomes: Made of DNA, humans possess 46 chromosomes per cell.

The Human Genome

  • Genome Project: Sequenced DNA constituents, revealing genetic connections to diseases.

    • Ability to identify genetic variations causing diseases.

    • Human Genome: Comprises over 3 billion base pairs (A, C, T, G).

    • Sequencing involves determining the order of these bases.

  • Genes: Approximately 30,000 genes serve as biological instructions for proteins.

    • Proteins are critical for physical structure, metabolic processes, and function regulation (e.g., enzymes).

Genetic Variations and Diseases

  • Misspellings in genetic sequences can lead to diseases.

    • Researchers compare DNA sequences from healthy and diseased individuals to identify such variations.

  • Over 6000 diseases linked to genetic mutations, including Huntington's disease and cystic fibrosis.

  • Common conditions (e.g., diabetes) involve complex interactions between genes and environmental factors.

Viruses: Structure and Function

  • Definition: Small infectious agents that require host cells for replication.

    • Comprised of nucleic acids (DNA/RNA) inside a protein coat.

  • Capsids: Complex structures made of capsomeres; some viruses possess additional membranes.

  • Bacteriophages: Viruses targeting bacteria, with distinct structural components (tail, collar).

Viral Replication Cycles

  • Lytic Cycle: Virus infects host, replicates, and new virions ultimately causes cell lysis, releasing .

  • Lysogenic Cycle: Virus integrates its DNA into the host chromosome, replicating silently and passing the viral DNA to daughter cells during replication.

Gene Therapy

  • Definition: Introducing new or modified genes into existing cells to treat diseases.

  • History: First authorized treatment on September 14, 1990, for ADA-SCID in Ashanti DeSilva.

Types of Gene Therapy

  • Somatic Cell Gene Therapy: Targets body (somatic) cells, non-heritable.

  • Germ Line Gene Therapy: Affects germ cells (sperm/eggs), inheritable but ethically controversial and currently not practiced.

Gene Therapy Approaches

  • In Vivo: Directly delivers therapeutic genes into patient tissues.

  • Ex Vivo: Cultures patient cells outside the body, modifies them, and then reinserts them.

Applications of Gene Therapy

  • Examples of Ex Vivo: Correction of ADA deficiency in SCID patients.

  • Examples of In Vivo: Cystic fibrosis treatment using adenovirus vectors to deliver CFTR genes.

Gene Therapy Vectors

  • Viral Vectors:

    • Retrovirus: Integrates into host genome; suited for dividing cells.

    • Adenovirus: Good for non-dividing cells, causing common cold.

    • Adeno-Associated Virus: Integrates into chromosome 19, nonpathogenic.

  • Non-Vectors:

    • Pure DNA Constructs: Low efficiency, require large doses.

    • Lipid-based Vectors: DNA surrounded by lipid layers; face degradation challenges.

    • Human Artificial Chromosomes: Carry large therapeutic genes.

Gene Therapy Techniques

  • Gene Gun: Shoots DNA-coated particles into cells.

  • Microinjection: Uses micropipettes to deliver substances into single cells.

  • Chemical Methods: Utilize agents to enhance DNA uptake in cells.

Types of Gene Therapy Strategies

  • Gene Augmentation: Replaces defective genes (e.g., p53 in liver cancer).

  • Gene Inhibition: Blocks overproduction of proteins using antisense or antigen approaches.

Advantages and Disadvantages of Gene Therapy

  • Advantages: Potential to cure hereditary diseases, transformative for conditions like heart disease and cancer. Provides options for future disease eradication.

  • Disadvantages: Short-lived results due to rapid cell division, risks of immune reactions, and limitations with multi-gene disorders.

Ethical Considerations of Gene Therapy

  • Unique ethical dilemmas arise, including:

    • Distinguishing between beneficial and harmful uses.

    • Economic disparities in access to therapies.

    • Potential societal impacts on acceptance of differences.

Conclusion

  • Gene therapy offers a potential lasting solution for genetic diseases but is currently expensive and complex. Ongoing advancements may one day enable widespread application in treating various conditions.