MCQ Quiz-RNA Therapeutics

MCQ Quiz: RNA Therapeutics

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RNA therapeutics have emerged as a revolutionary class of medicine, moving beyond targeting proteins to modulating gene expression directly at the RNA level. This approach allows for highly specific interventions for previously “undruggable” targets. For PharmD students, understanding the mechanisms of antisense oligonucleotides, siRNAs, and mRNA-based drugs is vital for counseling patients on these cutting-edge treatments and appreciating their profound impact on modern pharmacotherapy.

1. Which of the following best describes the general mechanism of antisense oligonucleotides (ASOs)?

  • They encode for a therapeutic protein
  • They bind to a specific mRNA sequence to block translation or promote degradation
  • They permanently edit the DNA sequence of a target gene
  • They act as catalytic enzymes to cleave proteins


Answer: They bind to a specific mRNA sequence to block translation or promote degradation

2. In the RNA interference (RNAi) pathway, what is the primary function of the RNA-induced silencing complex (RISC) after it is loaded with a small interfering RNA (siRNA)?

  • It transports the siRNA into the nucleus to alter the DNA
  • It acts as a template to produce a therapeutic protein
  • It binds to and cleaves the target mRNA molecule, preventing its translation
  • It adds a poly-A tail to the target mRNA to increase its stability


Answer: It binds to and cleaves the target mRNA molecule, preventing its translation

3. mRNA vaccines (e.g., for COVID-19) work by delivering mRNA that instructs host cells to produce a(n):

  • Therapeutic antibody
  • Viral antigen, which then stimulates an immune response
  • Functional human protein to correct a deficiency
  • Small interfering RNA to silence a viral gene


Answer: Viral antigen, which then stimulates an immune response

4. A major challenge for the therapeutic use of unmodified RNA molecules is their:

  • Extreme stability in the bloodstream
  • Inability to bind to any molecular target
  • Rapid degradation by ubiquitous nuclease enzymes
  • Tendency to spontaneously form DNA


Answer: Rapid degradation by ubiquitous nuclease enzymes

5. Nusinersen is an antisense oligonucleotide used to treat spinal muscular atrophy (SMA) by modulating the splicing of which pre-mRNA?

  • Dystrophin
  • CFTR
  • SMN2 (Survival of Motor Neuron 2)
  • Huntingtin


Answer: SMN2 (Survival of Motor Neuron 2)

6. What is the primary purpose of encapsulating mRNA or siRNA in lipid nanoparticles (LNPs)?

  • To make the drug solution visible
  • To protect the nucleic acid from degradation and facilitate its entry into cells
  • To give the drug a pleasant taste
  • To ensure the drug is cleared rapidly by the kidneys


Answer: To protect the nucleic acid from degradation and facilitate its entry into cells

7. Which enzyme in the natural RNAi pathway is responsible for dicing long double-stranded RNA into smaller siRNA molecules?

  • DNA Polymerase
  • Dicer
  • Helicase
  • Reverse Transcriptase


Answer: Dicer

8. Unlike siRNA, which typically leads to mRNA cleavage, microRNA (miRNA) most often regulates gene expression by:

  • Causing a frameshift mutation in the DNA
  • Inhibiting the translation of its target mRNA
  • Acting as a template for DNA synthesis
  • Binding directly to and inhibiting a protein


Answer: Inhibiting the translation of its target mRNA

9. The use of chemically modified nucleotides, like pseudouridine, in mRNA vaccines serves to:

  • Make the mRNA more visible under a microscope
  • Increase the mRNA’s stability and reduce its innate immunogenicity
  • Ensure the mRNA is integrated into the host cell’s DNA
  • Change the amino acid sequence of the resulting protein


Answer: Increase the mRNA’s stability and reduce its innate immunogenicity

10. Patisiran, a treatment for hereditary transthyretin-mediated (hATTR) amyloidosis, is what type of RNA therapeutic?

  • An mRNA vaccine
  • An antisense oligonucleotide
  • A small interfering RNA (siRNA)
  • An RNA aptamer


Answer: A small interfering RNA (siRNA)

11. RNA aptamers are short, single-stranded nucleic acid molecules that:

  • Encode for therapeutic proteins
  • Silence gene expression via the RISC pathway
  • Fold into specific 3D structures to bind to a target molecule, similar to an antibody
  • Catalyze biochemical reactions


Answer: Fold into specific 3D structures to bind to a target molecule, similar to an antibody

12. An antisense oligonucleotide can induce the degradation of its target mRNA by recruiting which endogenous enzyme?

  • RNA polymerase II
  • Dicer
  • RNase H
  • DNA ligase


Answer: RNase H

13. A key difference between RNAi (siRNA) and ASO therapies is that:

  • Only ASOs can be used to silence genes
  • RNAi utilizes the cell’s natural RISC machinery, often leading to catalytic target degradation
  • ASOs are typically double-stranded molecules
  • RNAi works by permanently editing the cell’s DNA


Answer: RNAi utilizes the cell’s natural RISC machinery, often leading to catalytic target degradation

14. The concept of “drug the messenger” is most applicable to which class of therapeutics?

  • Monoclonal antibodies
  • RNA-based drugs that target mRNA
  • Small molecule kinase inhibitors
  • Recombinant enzyme replacement therapies


Answer: RNA-based drugs that target mRNA

15. A major advantage of RNA therapeutics over traditional gene therapy is that they:

  • Do not typically alter the cell’s genomic DNA, avoiding risks of insertional mutagenesis
  • Have a much longer duration of action, often lasting a lifetime
  • Are much more stable in the body without a delivery vehicle
  • Can only be used to upregulate protein expression


Answer: Do not typically alter the cell’s genomic DNA, avoiding risks of insertional mutagenesis

16. Which of the following is a primary delivery challenge for RNA therapeutics targeting the liver?

  • The liver lacks the necessary machinery to process RNA
  • Getting the therapeutic past the Kupffer cells and into the hepatocytes
  • The blood-brain barrier prevents liver uptake
  • RNA drugs are preferentially taken up by muscle tissue


Answer: Getting the therapeutic past the Kupffer cells and into the hepatocytes

17. What is the mechanism of action for Pegaptanib, an RNA aptamer used for wet age-related macular degeneration (AMD)?

  • It silences the gene for VEGF
  • It encodes for a protein that breaks down abnormal blood vessels
  • It binds to and inhibits the protein VEGF
  • It repairs the damaged retina at the DNA level


Answer: It binds to and inhibits the protein VEGF

18. What does “off-target effects” refer to in the context of siRNA or ASO therapies?

  • The therapeutic fails to reach its intended tissue
  • The RNA molecule binds to and affects unintended mRNA sequences
  • The patient experiences an infusion reaction
  • The drug is cleared from the body too quickly


Answer: The RNA molecule binds to and affects unintended mRNA sequences

19. In contrast to mRNA vaccines, a potential future application of mRNA therapy is:

  • To silence a harmful gene
  • To provide a template for producing a functional protein in patients with a genetic deficiency
  • To create a permanent change in the patient’s DNA
  • To act as a competitive inhibitor of an enzyme


Answer: To provide a template for producing a functional protein in patients with a genetic deficiency

20. Chemical modifications to the sugar-phosphate backbone of ASOs (e.g., phosphorothioate linkages) are made primarily to:

  • Increase their susceptibility to nuclease degradation
  • Decrease their binding affinity to the target mRNA
  • Increase their resistance to nuclease degradation and improve their pharmacokinetic profile
  • Make them water-insoluble


Answer: Increase their resistance to nuclease degradation and improve their pharmacokinetic profile

21. A “dicer-substrate” siRNA is a design that:

  • Bypasses the Dicer enzyme completely
  • Is a slightly longer double-stranded RNA designed for more efficient processing by Dicer
  • Inhibits the function of the Dicer enzyme
  • Is a single-stranded RNA molecule


Answer: Is a slightly longer double-stranded RNA designed for more efficient processing by Dicer

22. Which of the following is NOT a type of RNA therapeutic?

  • Antisense oligonucleotide
  • Small interfering RNA
  • mRNA vaccine
  • Monoclonal antibody


Answer: Monoclonal antibody

23. The specificity of an ASO or siRNA drug is primarily determined by its:

  • Chemical backbone modifications
  • Delivery vehicle
  • Nucleotide sequence
  • Overall electrical charge


Answer: Nucleotide sequence

24. The duration of effect for an siRNA therapeutic is often long, requiring infrequent dosing, because:

  • The RISC complex is catalytically recycled after cleaving each target mRNA
  • The siRNA integrates into the host cell’s DNA
  • The siRNA is highly resistant to any form of degradation
  • The siRNA permanently binds to and inhibits the ribosome


Answer: The RISC complex is catalytically recycled after cleaving each target mRNA

25. A key difference between ASOs and siRNAs is that ASOs are typically __________ molecules, while siRNAs are __________ molecules.

  • single-stranded; double-stranded
  • double-stranded; single-stranded
  • protein; nucleic acid
  • circular; linear


Answer: single-stranded; double-stranded

26. Eteplirsen, used for Duchenne muscular dystrophy, is an ASO that works by:

  • Causing the degradation of the dystrophin mRNA
  • Blocking translation of the dystrophin mRNA
  • Modulating splicing to cause exon skipping, restoring the reading frame
  • Upregulating the production of a compensatory protein


Answer: Modulating splicing to cause exon skipping, restoring the reading frame

27. What is a “ribozyme”?

  • A protein enzyme that degrades RNA
  • A complex of RNA and protein
  • An RNA molecule that can act as a biological catalyst
  • A DNA molecule that binds to ribosomes


Answer: An RNA molecule that can act as a biological catalyst

28. Why is the liver a common target for RNA therapeutics?

  • It is not a common target due to poor blood flow
  • It is easily accessible from the bloodstream and naturally takes up nanoparticles
  • It lacks nuclease enzymes
  • It is the only organ with the RISC machinery


Answer: It is easily accessible from the bloodstream and naturally takes up nanoparticles

29. The therapeutic strategy of an mRNA vaccine is most analogous to:

  • Gene silencing
  • In-situ protein replacement therapy
  • Competitive enzyme inhibition
  • Antibody-drug conjugation


Answer: In-situ protein replacement therapy

30. Which cellular process do ASOs and siRNAs ultimately disrupt to achieve their effect?

  • DNA replication
  • Protein translation
  • Glycolysis
  • Apoptosis


Answer: Protein translation

31. GalNAc is a targeting ligand that can be conjugated to an siRNA to promote its uptake specifically by:

  • Muscle cells
  • Brain cells
  • Lung cells
  • Liver cells (hepatocytes)


Answer: Liver cells (hepatocytes)

32. One potential advantage of RNA therapeutics is their ability to target:

  • Only cell surface receptors
  • Any gene product, including historically “undruggable” proteins like transcription factors
  • Only bacterial proteins
  • Only viral enzymes


Answer: Any gene product, including historically “undruggable” proteins like transcription factors

33. The process of an ASO physically blocking the ribosome from proceeding along the mRNA is known as:

  • RNase H-mediated degradation
  • Splicing modulation
  • Steric hindrance or translational arrest
  • Aptameric binding


Answer: Steric hindrance or translational arrest

34. A self-amplifying mRNA (saRNA) vaccine contains not only the gene for the antigen but also genes for:

  • A viral replication machine
  • The RISC complex
  • The Dicer enzyme
  • An antibiotic resistance marker


Answer: A viral replication machine

35. A major reason for the rapid development of mRNA vaccines for COVID-19 was that:

  • The technology had been in development for many years prior
  • mRNA is extremely easy to handle and store
  • No clinical trials were required
  • The vaccines did not require a delivery vehicle


Answer: The technology had been in development for many years prior

36. A pharmacist counseling a patient on an RNA therapeutic would need to emphasize:

  • That the drug will permanently change their DNA
  • The specific storage requirements, as they are often fragile biologics
  • That the drug can be taken orally with food
  • That side effects are not possible with this class of drugs


Answer: The specific storage requirements, as they are often fragile biologics

37. The discovery of RNA interference (RNAi) in C. elegans by Fire and Mello was a landmark achievement that led to:

  • A Nobel Prize
  • The banning of all RNA research
  • The development of the first small molecule drug
  • The creation of the first antibiotic


Answer: A Nobel Prize

38. Which of the following is NOT a challenge for the delivery of RNA therapeutics?

  • Avoiding degradation by nucleases
  • Crossing the cell membrane
  • Escaping the endosome after cellular uptake
  • Their inherent ability to easily cross the blood-brain barrier


Answer: Their inherent ability to easily cross the blood-brain barrier

39. Volanesorsen is an ASO designed to treat familial chylomicronemia syndrome by reducing the production of which protein?

  • Transthyretin
  • Apolipoprotein C-III
  • SMN
  • VEGF


Answer: Apolipoprotein C-III

40. A circular RNA (circRNA) therapeutic is a novel concept that may offer what advantage over linear mRNA?

  • It is easier to synthesize
  • It lacks a cap and tail, potentially making it more resistant to exonucleases
  • It cannot be translated by ribosomes
  • It integrates into the host genome


Answer: It lacks a cap and tail, potentially making it more resistant to exonucleases

41. The development of RNA therapeutics relies heavily on an understanding of:

  • Protein chemistry
  • The genetic sequence of the target gene/mRNA
  • Organic synthesis
  • Human anatomy


Answer: The genetic sequence of the target gene/mRNA

42. Which property of RNA makes it a versatile therapeutic molecule?

  • It can carry genetic information and can also have structural or catalytic roles
  • It is a very simple and stable molecule
  • It is identical in structure and function to DNA
  • It is a type of protein


Answer: It can carry genetic information and can also have structural or catalytic roles

43. The “seed region” is a critical part of which type of RNA molecule for target recognition?

  • mRNA
  • rRNA
  • tRNA
  • microRNA (miRNA)


Answer: microRNA (miRNA)

44. A potential therapeutic strategy using RNA could be to deliver an mRNA encoding for a:

  • Monoclonal antibody, allowing the body to produce its own mAb therapy
  • Small interfering RNA
  • Cytotoxic small molecule
  • Viral capsid protein


Answer: Monoclonal antibody, allowing the body to produce its own mAb therapy

45. What is the fundamental difference between an RNA therapeutic and a small molecule drug like atorvastatin?

  • Small molecules are biologics, while RNA drugs are not
  • RNA drugs work via specific base-pairing to a nucleic acid target, while small molecules typically bind to protein pockets
  • RNA drugs are always administered orally
  • Small molecules do not have side effects


Answer: RNA drugs work via specific base-pairing to a nucleic acid target, while small molecules typically bind to protein pockets

46. Inotersen is an ASO that treats hATTR by:

  • Modulating splicing of the TTR gene
  • Causing the degradation of transthyretin (TTR) mRNA
  • Binding to and inhibiting the TTR protein
  • Delivering a functional copy of the TTR gene


Answer: Causing the degradation of transthyretin (TTR) mRNA

47. The “sense” strand of an siRNA duplex is the strand that:

  • Is degraded before RISC loading
  • Has a sequence corresponding to the target mRNA
  • Is also known as the guide strand
  • Binds to the ribosome


Answer: Has a sequence corresponding to the target mRNA

48. Why are ASO and siRNA drugs often referred to as “gene silencing” technologies?

  • They increase the amount of protein produced from a gene
  • They prevent or reduce the production of the protein encoded by the target gene
  • They physically remove the gene from the chromosome
  • They are only effective during cell division


Answer: They prevent or reduce the production of the protein encoded by the target gene

49. A major focus of ongoing research in RNA therapeutics is on developing:

  • New delivery systems to target tissues beyond the liver
  • RNA molecules that are less specific
  • Methods to make RNA integrate into DNA
  • Cheaper ways to synthesize proteins


Answer: New delivery systems to target tissues beyond the liver

50. The success of RNA therapeutics signifies a shift in drug development towards:

  • Exclusively using natural plant extracts
  • More personalized and information-based medicines
  • A complete halt in small molecule drug research
  • Therapies that are less specific and target multiple pathways


Answer: More personalized and information-based medicines

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