BIOTECG

What is gene therapy?

Technique to treat disease by altering genetic material.

In vivo vs Ex vivo gene therapy

In vivo delivers directly; ex vivo modifies cells outside the body.

Germline vs Somatic gene therapy

Germline affects heritable cells; somatic targets non-heritable body cells.

Four main viral vectors + one key trait each

Adenovirus (high capacity), AAV (low immunogenicity), γ-Retrovirus (dividing cells), Lentivirus (dividing + non-dividing cells).

What are viral episomes?

Independent circular DNA in host nuclei, characteristic of AAV.

Most widely used vector for in vivo gene therapy? Why?

AAV due to low immunogenicity and stable expression.

Major risk of integrating vectors (retro/lenti)?

Insertional oncogenesis can lead to leukemia.

Strimvelis – indication, vector, cell type, outcome

ADA-SCID; retroviral ex vivo; autologous CD34+ cells; approved in Europe.

Kymriah (CAR-T) – target & mechanism

Targets CD19 on B cells; engineered T cells attack cancer.

TCR vs CAR

TCR is MHC-dependent; CAR is MHC-independent.

Luxturna uses what vector and treats what?

Uses AAV vector for Leber Congenital Amaurosis.

Monoclonal vs Polyclonal antibodies

Monoclonal is from one clone; polyclonal is a mixture.

Antibody structure (heavy/light chains, Fab, Fc)

Two heavy and two light chains; Fab binds antigens, Fc has effector functions.

Five antibody classes

IgG, IgA, IgM, IgD, IgE.

Hybridoma technology – main steps

Immunize mouse, isolate B cells, fuse with myeloma, select hybridomas.

mAb types by origin (immunogenicity order)

Murine > Chimeric > Humanized > Fully Human.

Humira & Remicade – target & disease

Target TNF-α; treat autoimmune diseases.

Rituxan (Rituximab) – target & use

Targets CD20; treats B-cell lymphomas and rheumatoid arthritis.

Herceptin (Trastuzumab) – target & mechanism

Targets HER2; blocks signaling and promotes internalization.

Protein A chromatography

Purifies IgG by binding Fc region.

mAb naming: -xi- and -zu- mean what?

-xi- indicates chimeric; -zu- indicates humanized.

Purpose of vaccines

Train the immune system to recognize specific pathogens.

Four main types of vaccines

Live attenuated, inactivated, subunit, nucleic acid.

Live attenuated vaccine – pros, cons, example

Pros: strong immunity; cons: risk in immunocompromised; example: Oral Polio.

Inactivated vaccine – how made, example

Killed by heat or chemicals; example: Inactivated Polio.

Subunit (recombinant) vaccine – example

Only specific antigen produced; example: HPV Gardasil 9.

mRNA vaccine mechanism (Pfizer/Moderna)

Lipid nanoparticles deliver mRNA for antigen production.

Karikó & Weissman contribution

Modified mRNA to prevent inflammation, enabling safe vaccines.

Salk vs Sabin polio vaccine

Salk is inactivated; Sabin is live attenuated.

HPV vaccine – type & purpose

Recombinant subunit; prevents high-risk HPV strains.

Provenge (Sipuleucel-T) – what is it?

Therapeutic vaccine using patient dendritic cells for prostate cancer.

Vaccine Efficacy (VE) formula

VE = [(Attack rate unvaccinated − Attack rate vaccinated) / Attack rate unvaccinated] × 100.

Edward Jenner

Pioneered vaccination using cowpox to prevent smallpox.

Why are egg-based flu vaccines problematic?

Risk of mutations and allergies, slower production.