Biologic medicines for genetic disorders MCQs With Answer

Introduction: This quiz set on biologic medicines for genetic disorders is designed for M.Pharm students preparing for advanced exams and clinical practice. It covers mechanisms of therapeutic biologics — including enzyme replacement therapies, antisense oligonucleotides, RNA interference, viral vectors, and genome editing — plus delivery challenges, immunogenicity, pharmacokinetics, monitoring, and regulatory considerations. Questions emphasize conceptual understanding and application to real disorders such as lysosomal storage diseases, spinal muscular atrophy, Duchenne muscular dystrophy, and hemophilia. Use these MCQs to deepen your knowledge of molecular mechanisms, formulation and administration strategies, safety monitoring, and the translational steps from bench to bedside for biologic medicines targeting genetic diseases.

Q1. Which description best defines a “biologic medicine” used to treat genetic disorders?

• Low molecular weight synthetic small molecule designed to modify protein function
• Biologically derived therapeutic such as proteins, peptides, monoclonal antibodies, nucleic acids or viral vectors produced by living systems
• Inorganic compounds used as imaging agents in genetic disease diagnosis
• Dietary supplements that alter gene expression indirectly

Correct Answer: Biologically derived therapeutic such as proteins, peptides, monoclonal antibodies, nucleic acids or viral vectors produced by living systems

Q2. What is the primary mechanism of action of enzyme replacement therapy (ERT) in lysosomal storage disorders?

• Activation of endogenous gene transcription to increase enzyme synthesis
• Delivery of functional recombinant enzyme to replace the deficient or absent lysosomal enzyme
• Permanent correction of the mutated gene via integration into the genome
• Neutralization of circulating toxic metabolites without intracellular uptake

Correct Answer: Delivery of functional recombinant enzyme to replace the deficient or absent lysosomal enzyme

Q3. Which characteristic is an advantage of adeno-associated virus (AAV) vectors for in vivo gene therapy?

• Stable integration into the host genome ensuring transmission to daughter cells
• Large cargo capacity exceeding 10 kilobases for any gene
• Predominantly non-integrating behavior with efficient transduction of non-dividing cells and relatively low immunogenicity
• High risk of insertional oncogenesis compared with integrating retroviral vectors

Correct Answer: Predominantly non-integrating behavior with efficient transduction of non-dividing cells and relatively low immunogenicity

Q4. What is a defining feature of lentiviral vectors used in ex vivo gene therapy?

• They remain episomal and are rapidly lost from dividing cells
• They preferentially transduce only terminally differentiated neurons
• They integrate into the host genome enabling long-term expression in dividing cells
• They cannot carry therapeutic cDNAs larger than 1 kilobase

Correct Answer: They integrate into the host genome enabling long-term expression in dividing cells

Q5. How do antisense oligonucleotides (ASOs) commonly modulate gene expression in genetic diseases?

• By binding to DNA and promoting chromatin remodeling
• By binding to pre-mRNA or mRNA to alter splicing or induce RNase H-mediated degradation
• By inserting corrected gene copies into mitochondrial DNA
• By directly editing genomic DNA via double-strand breaks

Correct Answer: By binding to pre-mRNA or mRNA to alter splicing or induce RNase H-mediated degradation

Q6. Small interfering RNA (siRNA) therapeutic activity primarily depends on which cellular complex?

• Ribosome-associated chaperone complex
• RNA-induced silencing complex (RISC) that mediates target mRNA cleavage
• Proteasomal degradation machinery
• Mitochondrial RNA polymerase complex

Correct Answer: RNA-induced silencing complex (RISC) that mediates target mRNA cleavage

Q7. What is a major safety concern with CRISPR-Cas9 genome editing in therapeutic applications?

• Exclusive activity in mitochondrial genomes only
• Off-target DNA cleavage causing unintended insertions or deletions (indels) and potential genotoxicity
• Absolute inability to edit mammalian genomes
• Rapid degradation preventing any therapeutic effect

Correct Answer: Off-target DNA cleavage causing unintended insertions or deletions (indels) and potential genotoxicity

Q8. Exon skipping therapy for Duchenne muscular dystrophy (DMD) using antisense oligonucleotides aims to:

• Introduce a new exon to increase protein size beyond normal
• Cleave the dystrophin protein extracellularly to reduce toxicity
• Skip specific exons during pre-mRNA splicing to restore the reading frame and produce a truncated but functional dystrophin
• Promote permanent genomic deletion of the dystrophin gene

Correct Answer: Skip specific exons during pre-mRNA splicing to restore the reading frame and produce a truncated but functional dystrophin

Q9. Which approved therapy for spinal muscular atrophy (SMA) is an intrathecal antisense oligonucleotide?

• Onasemnogene abeparvovec
• Nusinersen
• Risdiplam
• Ivacaftor

Correct Answer: Nusinersen

Q10. What is a principal limitation of monoclonal antibodies when targeting genetic disease pathophysiology?

• They are readily taken up by all intracellular organelles
• They typically cannot cross cell membranes to reach intracellular targets, limiting them to extracellular or cell-surface molecules
• They always integrate into host DNA and alter gene sequences
• They universally elicit no immune response

Correct Answer: They typically cannot cross cell membranes to reach intracellular targets, limiting them to extracellular or cell-surface molecules

Q11. Formation of anti-drug antibodies (ADAs) against biologic therapies most commonly results in:

• Permanent cure of the genetic disorder
• Neutralization of therapeutic effect and/or hypersensitivity reactions
• Increase in oral bioavailability of the biologic
• Complete conversion of the biologic into a small molecule

Correct Answer: Neutralization of therapeutic effect and/or hypersensitivity reactions

Q12. Dosing of systemic AAV gene therapies is most commonly normalized and reported as:

• Milligrams per square meter of body surface area
• Vector genomes per kilogram of body weight
• International units per liter of plasma
• Micrograms per day administered orally

Correct Answer: Vector genomes per kilogram of body weight

Q13. How do biosimilars differ from generic small-molecule drugs?

• Biosimilars are chemically identical to the originator biologic
• Biosimilars are highly similar but not identical to reference biologics due to complex structures and manufacturing variability
• Biosimilars have identical manufacturing processes as the original company
• Biosimilars are always administered orally in tablet form

Correct Answer: Biosimilars are highly similar but not identical to reference biologics due to complex structures and manufacturing variability

Q14. What pharmacokinetic feature commonly explains the long half-life of therapeutic monoclonal antibodies?

• Rapid renal elimination due to small size
• FcRn-mediated recycling that protects IgG-based molecules from lysosomal degradation
• Extensive hepatic metabolism by CYP450 enzymes
• Complete excretion unchanged in bile within hours

Correct Answer: FcRn-mediated recycling that protects IgG-based molecules from lysosomal degradation

Q15. Which laboratory measure is most useful for monitoring clinical response to enzyme replacement therapy in lysosomal storage diseases?

• Serum creatinine concentration only
• Levels of accumulated substrate or disease-specific biomarkers and measurement of enzyme activity when feasible
• Random blood glucose at single time point
• Electrolyte panel without disease-specific markers

Correct Answer: Levels of accumulated substrate or disease-specific biomarkers and measurement of enzyme activity when feasible

Q16. What limits precise homology-directed repair (HDR)-based genome correction in many target tissues using CRISPR?

• HDR is highly active in non-dividing, post-mitotic cells
• HDR is efficient only in dividing cells, making precise correction difficult in many non-dividing tissues like muscle and neurons
• HDR does not require any repair template
• HDR always causes global hypomethylation of the genome

Correct Answer: HDR is efficient only in dividing cells, making precise correction difficult in many non-dividing tissues like muscle and neurons

Q17. Which genetic disorder is commonly treated with recombinant acid alpha-glucosidase enzyme replacement therapy?

• Hemophilia A
• Pompe disease
• Cystic fibrosis
• Spinal muscular atrophy

Correct Answer: Pompe disease

Q18. Ex vivo gene therapy is best described as:

• Direct in vivo injection of viral vectors into target tissue
• Modifying patient cells outside the body and then re-infusing the genetically modified cells into the patient
• Oral administration of plasmid DNA to correct germline mutations
• Topical application of antisense oligonucleotides to the skin

Correct Answer: Modifying patient cells outside the body and then re-infusing the genetically modified cells into the patient

Q19. Which chemical modification is commonly used to increase nuclease resistance and plasma stability of antisense oligonucleotides?

• Unmodified phosphodiester backbone with 2′-hydroxyl groups only
• Phosphorothioate backbone and 2′-O-modifications such as 2′-O-methyl or 2′-O-methoxyethyl
• Complete replacement of all nucleotides with amino acids
• Incorporation of viral capsid proteins into the oligonucleotide sequence

Correct Answer: Phosphorothioate backbone and 2′-O-modifications such as 2′-O-methyl or 2′-O-methoxyethyl

Q20. A critical regulatory manufacturing requirement for biologic medicines is:

• Production without any documented quality control to maximize speed
• Adherence to current Good Manufacturing Practice (cGMP) to ensure consistent quality, purity, potency, and traceability
• Use of non-sterile production facilities for faster turnaround
• Guarantee of zero variability between all production batches regardless of process controls

Correct Answer: Adherence to current Good Manufacturing Practice (cGMP) to ensure consistent quality, purity, potency, and traceability

Download