Targets for gene therapy MCQs With Answer

Targets for gene therapy MCQs With Answer

This quiz set is designed for M.Pharm students studying Molecular Pharmaceutics / NTDS (MPH 201T) and focuses on therapeutic targets used in gene therapy. The questions cover selection criteria for targets, classes of genes commonly targeted (monogenic disease genes, oncogenes, tumor suppressors, immune checkpoints, angiogenic factors), cellular and tissue accessibility, and special considerations like delivery barriers, off-target effects and mitochondrial targets. These MCQs probe conceptual understanding and clinical relevance, helping students prepare for advanced coursework and exams. Each question provides four options and the correct answer is indicated, enabling focused revision on realistic, exam-level topics in gene therapy target selection.

Q1. Which characteristic is most critical when selecting a gene as a target for replacement therapy in a monogenic recessive disorder?

• Gene size exceeding typical vector capacity
• Tissue-specific expression matching the disease phenotype
• Presence of multiple paralogues with redundant function
• High somatic mutation rate in the gene

Correct Answer: Tissue-specific expression matching the disease phenotype

Q2. For an autosomal dominant gain-of-function mutation, which gene therapy strategy is most appropriate?

• Gene addition of a wild-type copy
• Gene silencing or allele-specific knockdown
• Enhancement of promoter activity
• Overexpression of a paralogous gene

Correct Answer: Gene silencing or allele-specific knockdown

Q3. Which of the following is a common gene target class for cancer gene therapy aimed at restoring apoptotic control?

• Oncogenic receptor tyrosine kinases
• Tumor suppressor genes such as TP53
• Mitochondrial transfer RNAs
• Housekeeping metabolic enzymes

Correct Answer: Tumor suppressor genes such as TP53

Q4. Targeting VEGF in tumors is primarily intended to:

• Enhance tumor cell proliferation
• Block angiogenesis and reduce tumor blood supply
• Increase immune checkpoint expression
• Restore tumor suppressor function

Correct Answer: Block angiogenesis and reduce tumor blood supply

Q5. Which target is most suitable for liver-directed gene therapy using AAV vectors for a metabolic disorder?

• Brain-specific ion channels
• Hepatic enzymes such as factor IX or LDL receptor
• Cardiac sarcomeric proteins
• Immune checkpoint proteins on T cells

Correct Answer: Hepatic enzymes such as factor IX or LDL receptor

Q6. Why are mitochondrial DNA (mtDNA) mutations difficult to target with standard CRISPR-Cas9 approaches?

• mtDNA is too large for guide RNAs to recognize
• Guide RNAs and Cas9 are not efficiently imported into mitochondria
• mtDNA lacks coding sequences amenable to editing
• Mitochondria have robust DNA repair making editing ineffective

Correct Answer: Guide RNAs and Cas9 are not efficiently imported into mitochondria

Q7. Which target type is most appropriate for RNAi-based gene therapy?

• Defective structural proteins requiring full-length replacement
• Dominant-negative or overexpressed mRNAs causing pathology
• Non-coding regulatory DNA sequences
• Mitochondrial genome mutations

Correct Answer: Dominant-negative or overexpressed mRNAs causing pathology

Q8. When selecting a target for in vivo gene editing with CRISPR-Cas, which factor increases feasibility?

• Target gene resides in a highly repetitive genomic region
• Accessible cell type with low turnover and ability to be transduced
• Target requires multi-megabase replacement
• Therapeutic effect requires simultaneous modification of thousands of loci

Correct Answer: Accessible cell type with low turnover and ability to be transduced

Q9. Which receptor is a classical gene therapy target to lower plasma LDL cholesterol by gene addition?

• VEGFR2
• LDL receptor (LDLR)
• EGFR
• PD-1

Correct Answer: LDL receptor (LDLR)

Q10. In gene therapy for hemophilia B, the primary therapeutic target is:

• Clotting factor VIII deficiency correction
• Clotting factor IX gene addition to hepatocytes
• Platelet count enhancement via megakaryocyte modification
• Suppression of fibrinolysis pathway genes

Correct Answer: Clotting factor IX gene addition to hepatocytes

Q11. Which property makes a gene a poor target for viral vector-mediated gene therapy?

• Expression limited to a single accessible tissue
• Encoded cDNA size exceeding vector packaging limits
• Clear genotype–phenotype correlation
• Monogenic loss-of-function etiology

Correct Answer: Encoded cDNA size exceeding vector packaging limits

Q12. Targeting immune checkpoints (e.g., PD-1) in adoptive T cell gene therapy is intended to:

• Reduce T cell persistence and function
• Enhance T cell anti-tumor activity by preventing inhibition
• Promote tumor angiogenesis
• Induce global immunosuppression to prevent autoimmunity

Correct Answer: Enhance T cell anti-tumor activity by preventing inhibition

Q13. Which of the following targets is most appropriate for antisense oligonucleotide (ASO) therapy?

• Replacing a missing large structural protein
• Modulating splicing of a specific pre-mRNA to restore function
• Editing mitochondrial genome sequence
• Delivering transcription factors to the nucleus

Correct Answer: Modulating splicing of a specific pre-mRNA to restore function

Q14. Which target attribute increases the risk of off-target effects in genome editing?

• Unique sequence with no homology elsewhere in the genome
• Presence of multiple highly similar paralogous sequences
• Expression restricted to non-dividing cells
• Target located in a mitochondrial genome

Correct Answer: Presence of multiple highly similar paralogous sequences

Q15. For ocular gene therapy (e.g., RPE65-related retinal dystrophy), why is the retina a favorable target tissue?

• Systemic vector delivery is required for retinal transduction
• The eye is immune-privileged and accessible for local delivery
• Retinal cells are rapidly dividing, enabling efficient gene spread
• Retina has high rates of vector clearance making repeated dosing unnecessary

Correct Answer: The eye is immune-privileged and accessible for local delivery

Q16. Which gene therapy target approach is commonly used to treat hypercholesterolemia by reducing PCSK9 activity?

• Overexpression of PCSK9 in hepatocytes
• Gene silencing of PCSK9 via siRNA or ASO
• CRISPR-mediated insertion of PCSK9 promoter enhancers
• Increasing intestinal absorption of cholesterol

Correct Answer: Gene silencing of PCSK9 via siRNA or ASO

Q17. Which target selection consideration addresses safety concerns related to immune responses against transgene products?

• Selecting a transgene that is highly immunogenic in the patient population
• Using a transgene identical to endogenous self-protein when possible
• Delivering transgene systemically to generate tolerance
• Targeting only dividing cells to reduce exposure

Correct Answer: Using a transgene identical to endogenous self-protein when possible

Q18. Which of the following is an example of a non-ideal target for gene therapy due to complex polygenic contribution?

• Single-gene enzyme deficiency like phenylketonuria
• Multifactorial diseases like most forms of type 2 diabetes
• Monogenic dominant retinal dystrophy
• Hemophilia caused by single gene defects

Correct Answer: Multifactorial diseases like most forms of type 2 diabetes

Q19. In CAR-T cell therapies, which cellular target is typically engineered to recognize tumor-associated antigens?

• Patient hepatocytes
• Autologous T lymphocytes
• Bone marrow stromal cells
• Endothelial cells lining blood vessels

Correct Answer: Autologous T lymphocytes

Q20. Which statement best describes an ideal therapeutic gene target from a druggability perspective?

• Ubiquitously expressed, essential gene with multiple functions
• Tissue-specific gene where modulation yields a clear, measurable clinical benefit
• Highly polymorphic gene with unclear genotype–phenotype links
• Gene expressed only during embryogenesis

Correct Answer: Tissue-specific gene where modulation yields a clear, measurable clinical benefit

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