Virology Review 5 Word Scramble
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Question | Answer |
Gene Therapy | Introduction of DNA sequences into the cell of a patient with the aim of achieving a clinical benefit (fix something that is wrong) |
Gene Therapy in CA | Does not aim to restore normal function, the objective is to kill the CA cells |
Uses of Eukaryotic Virus Vectors | Gene Therapy, Recombinant vaccines, Anticancer agents |
Most common diseases addressed by gene therapy clinical trials | Cancer, vascular, & Monogenic diseases |
Most common gene types transferred in gene therapy clinical trials | Cytokine, Antigen, Tumor suppressor |
Most common vectors used in gene therapy clinical trials | Adenovirus, Retrovirus, Naked/Plasmid DNA |
2 Types of Gene Therapy | 1. Somatic cell gene therapy -- 2.Germ line gene therapy |
2 Methods of Delivery | IN VIVO therapy: patient is injected with the modified gene therapy vector -- & -- EX VIVO therapy: cells are removed, genes introduced, cells transplanted back into patient |
Chemical/Physical Methods of DNA Delivery Systems | Electroporation, Calcium Phophatases, Liposomes, Naked DNA gene gun |
Liposomes | Gold labeled DNA complexed with lipid, taken up via endocytic process |
liposomes advantage | works great in vivo because high production & effects dividing and non-dividng cells |
liposomes disadvantage | plasmid liposome complex vector cant specifically target a cell, less efficient, requires large amounts to acheive gene transfer |
Why use Viruses for Gene Therapy? | Experts at delivering genetic info to cells, we can Construct viruses for gene delivery, & different viruses target different tissues |
2 ways to prevent virus vectors from causing disease | 1.Engineer a non-pathogenic virus that expresses therapeutic gene -- 2.Engineer virus that requires a helper virus to replicate |
Technical Concerns | Regenerate a replication competent recombinant; Loss of therapeutic gene expression; Inadvertently transferring a contaminating gene or genes along with the therapeutic ones |
Technical Concerns: Loss of therapeutic gene expression | Many viruses limit gene expression to avoid the immune system. This can be avoided by using an inducible promotor. |
Gene therapy is difficult in differentiated/non-dividing cells | Many viruses only infect dividing cells. Avoid this by using retrovirus vectors that encode HIV integrase, which allows them to effectively infect nondividing cells |
Most popular Viral Vectors | Adenoviruses, Adeno-associated virus, Retroviruses, HSV, & Vaccinia |
Adenovirus Vectors | Infect dividing & nondividing cells. E1 is replaced with gene of interest. No integration. Severe risk of immune response |
AAV Vectors | non-pathogenic, infects dividing & nondiving cells, always integrates into chromosome 19, long term expression. BUT very small |
Retroviral Vectors | long term expression, can be pakaged with G protein of VSV so can infect many cell types, less immunogenic than adenovirus, integrates genome |
HSV Vectors | potential for nuerologic delivery, accepts large inserts, easy to manipulate, episomal latent infection can lead to long-term expression |
HSV & B-gal | B-gal replaces an essential immediate-early gene (replication deficient virus); HSV delivers B-gal reporter gene to neurons; can visually check for infection (blue) |
Vaccinia Virus Vectors | Virus replicates in cytoplasm, so low efficincy of passage of gene into nucleus |
Virotherpay | a therapy that seeks to harness the natural properties of viruses to aid in the fight against cancer |
Oncolytic Strategies | Virus surface altered so binds to CA cells only; virus is "armed" with extra genes to enhance effect; virus altered so can replicate in CA cells only |
Potential Oncolytic Viruses | Reovirus, Adenovirus, VSV, HSV, Vaccinia |
Adenovirall Vector CA Therapy | Find surface protein specific to CA |
Viruses, IFN, & CA Therapy | Many CA cells lack functional IFN rsponse, so more susceptible to some viruses. Would stay local & not infect other good tissues that have IFN response |
Created by:
lbr9349
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