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25 Cards in this Set
- Front
- Back
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Germ-line Genetic Therapy
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Genetic manipulation of germinal or reproductive cells
Therapeutic effect is permanent and transmissable. |
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Somatic Gene Therapy
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Insertion of genes into diploid cells of an individual where the genetic material is not passed to its progeny
Modifies specific cells or tissues |
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Ex vivo Delivery
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Transfer of genetic material into cells outside of body and then re-implanted
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Advantanges of Ex vivo delivery
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Lack of Immune Response
Enhanced efficacy of vector delivery in vitro |
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Disadvatages to Ex vivo delivery
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A small number of re-implanted cells remain viable (applicable to some diseases)
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In situ delivery
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Administering genetic material directly to the desired tissue when cells cannot be easily removed or reimplanted (brain cell)
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Advantages to In situ delivery
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Effective Targeting
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Disadvantages to In situ delivery
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Low efficiency of transduction
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In vivo delivery
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Genetic material is administered systemically
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Advantages to in vivo delivery
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Potentially the most useful
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Disadvantages to In vivo delivery
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Insufficient targting (prepared outside the body and the liver elimates most material on first pass)
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Retroviral Vectors
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Most widely used delivery vehicles
Relatively nonpathogenenic (exceptions include HIV) Use RNA as their genetic material Can infect a variety of cells and can integrate their genome into a single RANDOM site (possible to develop side effects since you can't specify where you want it to go) Integration is only possible in dividing cells since membrane is permeable during cell division -Can incorporate about 8kb of transgene DNA |
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Advantages to Retroviral Vectors
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Stable and efficient integration into the genome
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Disadvantages to Retroviral Vectors
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Integrate randomly into the host genome possibly near a proto-oncogene leading to tumor formation
Difficult to produce in high concentrations Induce an immune response |
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Adenoviruses
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Most common DNA virus used for gene therapy
Target both dividing and nondividing cells but unable to integrate into host genome. Do not produce serious illnesses Can cause upper respiratory tract infections Virus is eliminated from nucleus over time -->repeated dosing in necessary -Most have a transgene capacity of 7kb newer versions can hold 35kb "gutless or pseudo" |
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Advantages of Adenoviral Vectors
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They can produce a high titer of purified particles
Can infect a variety of cells Especially good for lung cells and have ben used to treat cystic fibrosis |
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Disadvantages of Adenoviral Vectors
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Highly immunogenenic which limits their repeated dosing
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Adeno-Associated Viral Vectors (AAV)
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No known pathogeneic effect on humans
Single stranded DNA - need an adeno or herpes helper virus to replicate Integrates on a chromosome 19q with no noticeable effects on other genes Weak immunogens in most tissues |
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Advantages to AAV's
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Selective integration into host genome and no risk of insertional mutagenesis
Long-term expression |
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Disadvantages to AAV's
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The production of the viral partilces is a complicated process
Limited capacity |
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Lentiviruses
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Specialized retroviruses that can infect both dividing and nondividing cells
Integrate into host genome at a random site Human HIV is the basis for most lentiviral vectors |
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Advantages to Lentiviruses
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Long-term expression
Infection of nondividing cells |
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Disadvantage to Lentiviruses
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Risk of insertional mutagenesis
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Herpes Simplex Viral Vectors (HSV)
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Complex, double stranded DNA viruses
Viral genome does not integrate into host genome Can establish life long latency in sensory ganglia |
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Advantages to HSV Vectors
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Specially suited for CNS treatment due to long term expression
Can express large transgenes No risk of insertional mutagenesis |
