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23 Cards in this Set
- Front
- Back
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What is gene therapy used to describe?
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treatment of any disorder, genetic or acquired, using genetic therapy
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What are 4 parts of the strategy for gene therapy
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Identify genetic basis for disease
Develop rational genetic treatment target gene to cells express gene appropriately -- alter expression of target gene |
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What are 2 methods of delivering genetic therapies?
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Ex vivo - take cells out, manipulate them, inject into site
In vivo/in situ - administer alteration directly into the area |
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What are the two general types of vectors used to target genes to cells?
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viral and non viral
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What viral vectors came from HIV? Which are DNA based?
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Retrovirus, Lentivirus
DNA based - adenovirus, herpes simplex virus |
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What are advantages and disadvantages of viral vectors?
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adv: high level of gene transfer and expression, many can infect non-dividing cells many can incorporate into host genome
disadv: inflammatory response, immunological response, hard to work with, danger of contaminating viruses |
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What are non-viral vectors?
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injection of DNA without a virus. Has other types but basically naked DNA with some type of coating
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What are advantages and disadvantages of non-viral vectors?
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Adv: non-immunogenic, non-inflammatory, easy and cheap to produce
Disadv: Low gene transfer and expression, only short term expression (does not integrate into genome) |
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What is a gene promoter?
Tissue specific e.g.? Inducible e.g. |
a DNA sequence that drives gene expression..
T: alpha actin promoter in Smooth m. vWF promoter in endothelial cells Inducible: chemical (steroids) hypoxia (low O2) |
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What gene will prevent smooth muscle proliferation after injury?
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P21
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What was the first genetic disease mechanism that was identified?
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sickle cell disease - mutant hemoglobin
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What causes SCID?
Hypercholesterolemia? |
SCID - mutant common gamma chain protein on immune cells
LDL receptor deficiency |
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What are genetic treatments for:
1. Sickle cell Disease 2. Cystic fibrosis 3. XSCID 4. Cancer |
1. Increase fetal hemoglobin
2. Replace CFTR gene 3. Replace common gamma chain protein expression 4. anti-proliferative agents (TNF,IFN), immune regulators (cytokines), lethal genes |
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What are barriers to gene transfer?
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Body - serum factors, biodistribution "first pass organs", immune system
Cellular barrier - membranes |
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What does serum do and how does it achieve this?
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Protects the body via nuclease (destroy DNA, RNA), Opsins (target for macrophages), aggregation
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Why is biodistribuiton important?
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First pass organs (liver lungs spleen) might accumulate the delivered genes which decreases the delivery to target organs
thus gene delivery is not universal |
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What is ectopic synthesis of therapeutic proteins?
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making a protein in a different tissue than where it is normally made to address the problem. Example is alpha-1 antitrypsin can be produced in smooth m. to prevent autodigestion
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What is an anti-sense oligonucleotide?
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A gene (RNA) that is delivered that binds to mRNA causing cleavage. it prevents translation
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How does RNA interference work?
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Dicer cleaves dsRNA. THe pieces called small interferring RNA siRNA, are recognized by RISC (RNA induced silencing complex) RISC uses si RNA to bind and degrade mutant mRNA
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What is the problem with anti-sense oligonucleotides and RNA interference?
Benefit of trans-splicing ribozymes? |
Have to provide ongoing doses 1:1 ration
1: many ratio so will not have to prescribe such great quantities |
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What are trans-splicing ribozymes?
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a ribozymes that can be created that automatically digests mutant mRNA
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What are DNA vaccines made from?
What is an advantage to a DNA vaccine? |
dead or weak viruses or bacteria or modified toxins
Polio, DPT, MMR, Smallpox It will be very cheap to produce and speedy to give |
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What are the delivery methods for genetic therapy?
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naked DNA, liposomes, synthetic polymers, sound waves,electric fields, and guns
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