Gene therapies flashcards
1
Q
What are the main processes in the flow of genetic information?
A
- Transcription: DNA → mRNA (occurs in the nucleus).
- Translation: mRNA → Protein (occurs in ribosomes in the cytosol).
- DNA contains the genetic code shared by all somatic cells, while specific mRNAs transcribed define cell functions.
2
Q
What causes genetic disorders?
A
- Single-gene inherited disorders (e.g., cystic fibrosis, muscular dystrophy).
- Polygenic diseases or acquired mutations during cell replication.
- Mutations often lead to non-functional proteins, disrupting cellular pathways and causing disease.
3
Q
How do gene therapies differ from conventional therapeutics?
A
- Conventional drugs target proteins or protein pathways but don’t address the underlying genetic causes.
- Gene therapies aim to replace or modify faulty genes, enabling cells to produce functional proteins and address root causes.
4
Q
What are the types of nucleic acid medicines?
A
- DNA: Used for genome modification or gene replacement.
- mRNA: Provides transient protein expression.
- siRNA: Silences specific genes via double-stranded RNA mechanisms.
- miRNA: Regulates gene expression via single-stranded RNA.
5
Q
What are DNA-based therapies, and how do they work?
A
- Deliver therapeutic DNA to cells, often via plasmids.
- Replace or augment faulty genes, enabling cells to produce functional proteins.
- Target genetic disorders without existing treatments.
6
Q
What are the main gene delivery systems?
A
- Viral Vectors: Commonly adeno-associated viruses (AAVs), with high transfection efficiency and low immunogenicity but high production costs and risks of immune responses.
- Non-Viral Methods: Include direct injection, gene guns (gold-particle bombardment), and electroporation (membrane permeabilization with electric pulses).
7
Q
What is the difference between in vivo and ex vivo gene therapies?
A
- Ex Vivo: Cells are extracted from the patient, genetically modified outside the body, and then reintroduced.
- In Vivo: Therapeutic DNA is directly delivered to the patient’s cells.
8
Q
Give examples of DNA-based therapies.
A
- Luxturna: Treats retinal diseases caused by RPE65 mutations via single retinal injections.
- Zolgensma: Treats spinal muscular atrophy by delivering the SMN1 gene via AAV vectors.
9
Q
What are the ethical considerations in gene therapy?
A
- Somatic Cell Therapy: Changes are confined to the treated individual.
- Germline Therapy: Modifications affect future generations and raise concerns about consent, unintended consequences, and misuse (e.g., designer babies).
10
Q
What are the structural components of mRNA?
A
- 5’ Cap: Facilitates ribosome attachment.
- Untranslated Regions (UTRs): Enhance mRNA stability and translation.
- PolyA Tail: Prevents degradation and stabilizes mRNA.
11
Q
What are the advantages of mRNA-based therapies?
A
- Transient protein expression avoids risks of genome integration.
- Synthetic production allows rapid scalability.
- Adaptable design for updates, e.g., in mRNA vaccines for emerging viral variants.
12
Q
What role do modified nucleotides play in mRNA therapies?
A
- Modified nucleotides, like pseudouridine, reduce inflammatory responses.
- Enhance translation efficiency and stability of synthetic mRNA.
- Work by mimicking natural nucleotides, reducing immune activation.
13
Q
What are the key delivery systems for mRNA?
A
- Lipid Nanoparticles (LNPs):
- Ionizable lipid: Encapsulates mRNA.
- Phospholipids: Stabilize the lipid bilayer.
- Cholesterol: Improves fluidity.
- PEG lipids: Stabilize particles for storage.
- Polymeric Systems: Use polymers to form complexes with mRNA for delivery.
14
Q
What are some clinical applications of mRNA therapies?
A
- Cystic Fibrosis: mRNA encoding CFTR gene under development for lung delivery.
- Cardiac Failure: VEGF mRNA enhances vascular regeneration post-heart attack.
- COVID-19 Vaccines: Revolutionized infectious disease immunization, demonstrating rapid adaptability to viral mutations.
