mRNA Vaccines and Therapeutics Overview
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Questions and Answers

What effect does extending the length of the poly(A) tail have on protein levels in UMR-106 cells?

  • Protein levels decrease from the onset with longer tails.
  • Protein levels peak at 60 residues of the poly(A) tail. (correct)
  • Protein levels increase continuously with tail length.
  • Protein levels are unaffected by the poly(A) tail length.

    • How does the type of cell affect the maintenance of long poly[d(A/T)] sequences?

  • Cell type has no effect on the maintenance of sequences.
  • All cell types can easily maintain long sequences.
  • Long sequences are maintained better in certain mammalian cells.
  • The ability to maintain sequences varies with the bacterial strain. (correct)

    • What is one reason that about one third of mRNA molecules are not translated?

  • They lack methylation at their cap base. (correct)
  • They have a reverse orientation.
  • They are shorter than expected.
  • They are contaminated with DNA.

    • Which elements were combined in Sahin's study to enhance translational efficiency?

    <p>The α globin 3'-UTR and β globin 5'-UTR.</p> Signup and view all the answers

    What issue arises from the use of regular cap analogs in mRNA transcription?

    <p>They can be incorporated in reverse orientation.</p> Signup and view all the answers

    What was notable about the protein expression when using mRNA capped with a phosphorothioate modified anti-reverse cap?

    <p>Protein expression peaked at 8 hours and persisted for 72 hours.</p> Signup and view all the answers

    Which method allows transcription of mRNA without a cap that can later be added?

    <p>Transcribing with a vaccinia virus capping complex.</p> Signup and view all the answers

    What was the result of transfecting dendritic cells with mRNA containing a longer transcribed poly(A) tail?

    <p>A substantial improvement in protein expression was observed.</p> Signup and view all the answers

    What contaminants may interfere with the purity of mRNA samples?

    <p>Shorter and longer unintended transcripts.</p> Signup and view all the answers

    What is the purpose of ‘anti-reverse’ cap analogs (ARCAs)?

    <p>To produce mRNA with caps in the correct orientation.</p> Signup and view all the answers

    What primary activity of bacteriophage polymerases can complicate mRNA production?

    <p>RNA-dependent RNA polymerase activity.</p> Signup and view all the answers

    What enzymatic activity does the vaccinia virus capping complex NOT contain?

    <p>DNA polymerase.</p> Signup and view all the answers

    What is a potential downside to using ARCAs in mRNA production?

    <p>They can complicate purification steps.</p> Signup and view all the answers

    What is the role of phosphorothioate cap analogs in mRNA?

    <p>They stabilize mRNA and increase translational efficiency.</p> Signup and view all the answers

    What is the main focus of the research mentioned regarding secondary structure in eucaryotic mRNAs?

    <p>Inhibiting translation through secondary structure.</p> Signup and view all the answers

    Which of the following is true regarding replicable and recombinogenic RNAs?

    <p>They can facilitate genetic recombination.</p> Signup and view all the answers

    How does a short leader sequence affect translation fidelity according to the findings?

    <p>It impairs the fidelity of translation.</p> Signup and view all the answers

    What mechanism of mRNA turnover is mentioned in the context of nucleases and decapping enzymes?

    <p>Degradation of mRNA molecules.</p> Signup and view all the answers

    What is the primary function of RIG-I in the immune response?

    <p>To recognize uncapped RNA molecules with a 5'-triphosphate moiety</p> Signup and view all the answers

    Which characteristic does MDA5 use to discriminate between RNA molecules?

    <p>The 2'-O-methylation status of the cap structure</p> Signup and view all the answers

    Which other proteins are part of the receptor family that includes RIG-I?

    <p>MDA5 and LGP2</p> Signup and view all the answers

    What effect does a single intramuscular injection of Epo-encoding mRNA have in BALB/c mice?

    <p>Promotes the expression of functional Epo</p> Signup and view all the answers

    What remains a matter of debate regarding RNA-based vaccines?

    <p>The role of non-TLR RNA-sensors in immunostimulation</p> Signup and view all the answers

    What is a key feature of mRNA vaccines regarding genomic interaction?

    <p>They do not interact with the genome.</p> Signup and view all the answers

    Which immune response capability is highlighted for mRNA vaccines?

    <p>Both cellular and humoral immunity.</p> Signup and view all the answers

    What is a safety characteristic of mRNA as a vector?

    <p>It is an intrinsically safe vector.</p> Signup and view all the answers

    What does the flexibility of mRNA vaccines allow regarding the production process?

    <p>Production of various proteins without adjustments.</p> Signup and view all the answers

    In terms of production efficiency, how do mRNA-based therapeutics benefit compared to DNA?

    <p>They are less costly and time-consuming.</p> Signup and view all the answers

    What aspect of mRNA provides an advantage over traditional vaccine platforms?

    <p>It is a transient carrier of information that can encode diverse proteins.</p> Signup and view all the answers

    Which of the following diseases can mRNA vaccines potentially combat?

    <p>Specific cancers and infections.</p> Signup and view all the answers

    What is one of the major advantages of using mRNA as a vaccine platform compared to DNA?

    <p>mRNA does not need to cross cell membranes.</p> Signup and view all the answers

    Study Notes

    mRNA Vaccines and Therapeutics

    • mRNA is a promising vector for vaccines due to its safety, flexibility, and ability to induce a balanced immune response.
    • mRNA vaccines are non-replicative, metabolically decaying within days, making them a transient carrier of information.
    • Production and application of mRNA vaccines offer flexibility for development, allowing for the encoding and expression of any protein.
    • mRNA vaccines can be used to fight diseases like infections and cancer, as well as for protein replacement therapies.
    • mRNA vaccines don't require adjustments to the production process for different protein targets, allowing for cost and time savings.
    • mRNA-based vaccines offer increased efficacy compared to DNA-based vaccines, as they don't need to cross the nuclear envelope.

    mRNA Modifications for Improved Efficiency

    • The regular cap analog (m7G) is sometimes incorporated in the reverse orientation, leading to unmethylated caps and lack of translation.
    • To avoid unmethylated caps, mRNA can be transcribed without a cap analog and subsequently capped using the vaccinia virus capping complex, which adds a natural cap.
    • "Anti-reverse" cap analogs (ARCAs) can be used to ensure the cap is in the correct orientation, leading to improved protein expression.
    • Extending the poly(A) tail length can improve translational efficiency, however, maintaining long poly[d(A/T)] sequences is challenging.

    mRNA Stability and Translational Efficiency

    • The use of 5' and 3' untranslated regions (UTRs), specifically those from the β globin gene, can enhance translational efficiency and mRNA stability.
    • Combinations of UTRs, long poly(A) tails, and phosphorothioate modifications can further enhance translational efficiency.

    mRNA Adjuvanticity

    • mRNA can be a potent adjuvant due to its inherent immunostimulatory properties.
    • Cytoplasmic RNA sensors, such as RIG-I, MDA5, and LGP2, recognize uncapped RNA molecules and trigger immune responses.
    • Other RNA sensors, like PKR and 2'-5'-oligoadenylate synthetase, can also contribute to immunostimulation.

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    Developing mRNA-Vaccine Technologies PDF

    Description

    Explore the innovative world of mRNA vaccines and therapeutics. This quiz covers the advantages of mRNA as a vaccine vector, its applications in various diseases, and modifications that enhance its efficacy. Test your knowledge on how mRNA technology is transforming modern medicine.

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