Biologics: gene therapy MCQs With Answer

Biologics: Gene Therapy MCQs With Answer is designed for M.Pharm students studying Biological Evaluation of Drug Therapy. This focused quiz collection covers core concepts in gene therapy including vector biology, delivery strategies, genome editing tools (CRISPR/Cas, base and prime editors), safety concerns such as insertional mutagenesis and immunogenicity, regulatory and GMP considerations, potency and biodistribution testing, and clinical applications like CAR‑T and AAV-mediated replacement. Each question challenges you to apply mechanistic knowledge to practical scenarios encountered in development and evaluation of gene therapeutics. Use these MCQs to assess readiness for exams and to deepen understanding of translational issues in modern biologic drug development.

Q1. What is the primary definition of gene therapy?

• Administration of small molecule drugs to modulate gene expression
• Introduction, modification, or replacement of genetic material to treat or prevent disease
• Use of monoclonal antibodies to neutralize pathogenic proteins
• Vaccination with attenuated pathogens to induce immunity

Correct Answer: Introduction, modification, or replacement of genetic material to treat or prevent disease

Q2. Which statement correctly distinguishes somatic from germline gene therapy?

• Somatic gene therapy targets reproductive cells and is heritable
• Somatic gene therapy modifies non-reproductive cells and changes are not transmitted to offspring
• Germline therapy modifies only mature somatic tissues and is reversible
• Germline therapy is routinely used in clinical practice for adults

Correct Answer: Somatic gene therapy modifies non-reproductive cells and changes are not transmitted to offspring

Q3. Which best describes an ex vivo gene therapy approach?

• Direct injection of viral vectors into patient tissues without cell manipulation
• Modifying patient cells outside the body and returning the engineered cells to the patient
• Systemic delivery of naked plasmid DNA by intravenous injection
• Using small interfering RNA applied topically to a lesion

Correct Answer: Modifying patient cells outside the body and returning the engineered cells to the patient

Q4. Which viral vector is known for stable integration into the host genome and is commonly used for ex vivo gene delivery?

• Adeno-associated virus (AAV)
• Lentiviral vectors
• Adenoviral vectors
• Herpes simplex virus vectors

Correct Answer: Lentiviral vectors

Q5. Which characteristic is most accurately associated with recombinant AAV vectors?

• High frequency random genomic integration and strong oncogenic risk
• Large packaging capacity greater than 10 kb
• Predominantly episomal persistence with low integration frequency and relatively low immunogenicity
• Replication-competent and used for systemic high-dose therapies without safety concerns

Correct Answer: Predominantly episomal persistence with low integration frequency and relatively low immunogenicity

Q6. Historically which vector class caused insertional mutagenesis leading to leukemia in some early trials?

• Adeno-associated virus vectors
• Lentiviral vectors
• Gamma-retroviral vectors
• Non-viral lipid nanoparticles

Correct Answer: Gamma-retroviral vectors

Q7. What is the primary molecular mechanism by which CRISPR-Cas9 edits genomic DNA?

• Single-strand nicks repaired solely by base excision repair
• Double-strand DNA breaks repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR)
• RNA-guided methylation without altering DNA sequence
• Insertion of viral transgenes using integrases

Correct Answer: Double-strand DNA breaks repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR)

Q8. Which strategy is most effective to reduce off-target editing by CRISPR systems?

• Use of high-fidelity Cas variants and optimized guide RNAs
• Increasing Cas9 and guide RNA concentrations indefinitely
• Delivering CRISPR components as continuous expressing plasmids
• Avoiding guide RNA design algorithms

Correct Answer: Use of high-fidelity Cas variants and optimized guide RNAs

Q9. What describes the core concept of CAR‑T cell therapy?

• Infusion of unmodified donor T cells to treat infections
• Autologous T cells engineered to express chimeric antigen receptors targeting tumor antigens
• Use of monoclonal antibodies to recruit complement against cancer cells
• In vivo delivery of cytokine genes to boost immunity

Correct Answer: Autologous T cells engineered to express chimeric antigen receptors targeting tumor antigens

Q10. Which is a major barrier to systemic re-administration of AAV-based gene therapies?

• Rapid renal clearance of AAV particles
• Pre-existing or therapy-induced neutralizing antibodies and cellular immune responses
• Unlimited payload capacity enabling immune evasion
• AAV integration into germline cells

Correct Answer: Pre-existing or therapy-induced neutralizing antibodies and cellular immune responses

Q11. In the context of gene therapy product release, what does a potency assay measure?

• Only the chemical impurities present in the final formulation
• The biological activity of the gene therapy product in a relevant cell-based or functional assay
• The visual clarity and color of the vector suspension
• The administrative cost of manufacturing

Correct Answer: The biological activity of the gene therapy product in a relevant cell-based or functional assay

Q12. Why is GMP manufacturing critical for viral vector-based gene therapies?

• GMP lowers production costs but is optional for clinical use
• GMP ensures consistency, purity, potency and safety required for clinical and regulatory acceptance
• GMP guarantees zero immunogenicity of products
• GMP eliminates the need for clinical trials

Correct Answer: GMP ensures consistency, purity, potency and safety required for clinical and regulatory acceptance

Q13. What is the primary purpose of biodistribution studies in preclinical gene therapy development?

• To determine the cost-effectiveness of the manufacturing process
• To map vector distribution and assess off-target transduction and potential toxicities in tissues
• To evaluate taste and odor profiles of the final product
• To demonstrate immediate clinical efficacy in patients

Correct Answer: To map vector distribution and assess off-target transduction and potential toxicities in tissues

Q14. What biosafety level (BSL) practices are typically recommended for routine handling of replication-defective AAV vectors in a research setting?

• Biosafety level 4 (BSL-4) with full positive-pressure suits
• Biosafety level 2 (BSL-2) practices with appropriate PPE and training
• No biosafety measures are necessary for AAV
• Biosafety level 1 (BSL-1) with no containment

Correct Answer: Biosafety level 2 (BSL-2) practices with appropriate PPE and training

Q15. Before initiating first-in-human clinical trials of a gene therapy, which regulatory submission is typically required?

• New Dietary Ingredient (NDI) notification
• Investigational New Drug (IND) application or equivalent submission to the regulatory authority
• Abbreviated New Drug Application (ANDA)
• Post-marketing surveillance report

Correct Answer: Investigational New Drug (IND) application or equivalent submission to the regulatory authority

Q16. How does prime editing differ from classical CRISPR-Cas9 editing?

• Prime editing only introduces random insertions via viral integrases
• Prime editing can make targeted insertions, deletions and precise base changes without creating double-strand breaks
• Prime editing uses RNA interference to silence genes
• Prime editing always requires a donor viral vector for integration

Correct Answer: Prime editing can make targeted insertions, deletions and precise base changes without creating double-strand breaks

Q17. Which analytical attribute is most important to quantify when releasing an AAV therapeutic lot?

• Protein molecular weight by mass spectrometry only
• Vector genome titer (vg/mL)
• Blood glucose levels of manufacturing staff
• Colorimetric pH indicator strip reading only

Correct Answer: Vector genome titer (vg/mL)

Q18. What is the immunological challenge specifically associated with repeated systemic dosing of viral vector gene therapies?

• Induction of tolerance allowing higher subsequent doses
• Generation of neutralizing antibodies that block re-dosing and may cause adverse immune reactions
• Enhanced vector transduction on subsequent doses due to priming
• Complete elimination of all transduced cells after first dose

Correct Answer: Generation of neutralizing antibodies that block re-dosing and may cause adverse immune reactions

Q19. Which clinical indication is most suitable for classic gene replacement therapy?

• Complex polygenic disorders with strong environmental modulation
• Loss-of-function monogenic disorders such as hemophilia B or severe combined immunodeficiency
• Acute bacterial infections responsive to antibiotics
• Behavioral disorders with multifactorial etiology

Correct Answer: Loss-of-function monogenic disorders such as hemophilia B or severe combined immunodeficiency

Q20. Why are long-term follow-up (LTFU) studies required for many gene therapy trials?

• To meet marketing requirements for unrelated products
• To monitor for delayed adverse events, persistence of expression, and potential insertional oncogenesis over time
• Because short-term data are always sufficient to demonstrate safety
• To avoid reporting any adverse events occurring after one year

Correct Answer: To monitor for delayed adverse events, persistence of expression, and potential insertional oncogenesis over time

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