Lecture 20 - Viral Vectors & Gene Therapy 2 Flashcards
(15 cards)
What is Choroideremia?
An incurable X-linked recessive disorder that causes progressive vision loss due to mutations in the CHM gene on the X-chromosome.
What causes Choroideremia?
Mutations in the CHM gene encode for Rab escort protein-1 (REP-1), leading to loss of retinal cells and progressive vision loss.
What is the gene therapy for Choroideremia?
Involves putting normal copies of CHM/REP1 gene back into retina cells using viral vectors.
What viral vector is used for Choroideremia gene therapy?
Adeno Associated Virus vector AAV (serotype 2) containing a REP-1 transgene encoded by the CHM gene.
What are the advantages of AAV vectors?
- Non-integrative, 2. Infects both dividing & non-dividing cells, 3. Transient expression, 4. Different serotypes have tropism, 5. Do not elicit an immune response.
What is the mechanism of gene therapy for Choroideremia?
Involves gene addition strategy by introducing a functional copy of the REP1 protein into the retina.
What is the delivery method for AAV2 REP1 vector?
In situ delivery by injecting the AAV2 vector into the retina.
Is the gene therapy for Choroideremia a viable long-term treatment?
Yes, it targets non-dividing cells, allowing persistence of expression and stable production of REP1 protein.
What is Sickle Cell Disease (SCD)?
A genetically inherited RBC disorder affecting the beta-globin subunits of hemoglobin, resulting in malformed RBCs.
What are current treatments for SCD?
Blood transfusions, pharmacological drugs (Hydroxyurea), and bone marrow transplants.
What are the two groups of SCD gene therapy?
- Lentiviral-based gene therapies, 2. Genome editing-based gene therapies.
What is Lyfgenia?
FDA Approved gene therapy for SCD using a lentiviral vector containing an ‘anti-sickling’ B-globin transgene.
What is the mechanism of SCD gene therapy?
Inhibits polymerisation of sickled hemoglobin tetramers through modifications of the mutated beta-globin transgene.
What is the delivery method for SCD gene therapy?
Ex vivo gene delivery involving packaging transgene into viral particles and modifying hematopoietic stem cells.
Does SCD gene therapy provide a long-term treatment strategy?
Yes, it offers long-term and stable expression of the anti-sickling beta globin transgene.
