Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
24 Cards in this Set
- Front
- Back
|
What is gene replacement therapy?
|
The replacement of a defective gene w/ a normal copy of the same gene. Tech diff to achieve b/c targeted insertion is inefficient
|
|
|
What is gene augmentation theray?
|
The transfer of a normal copy of a gene into a cell that has a defective copy of the gene. Mucheasier to achieve b/c targeted insertion is inefficient
|
|
|
What is gene regulation therapy?
|
The use of antisense DNA oligonucleotides, small inactivating RNA (siRNA) or shall hairpin (shRNA) to inactivate specific mRNA. Organ or tissue specific inactivation of a particular mRNA is hard to achieve
|
|
|
What are some candidate diseases for gene therapy?
|
Genetic: SCID, hemophilia, CF, thalassemias, sickle cell,inherited emphysema. Acquired: Cancer, Parkinson's, Alzheimer's, atherosclerosis, asthma)
|
|
|
Approaches to gene transfer?
|
ex vivo: cells w/ defective gene removed form patient, gene transferred into cells, cells transplanted back into patient. in vivo: gene transfer directly into patient
|
|
|
Vehicles for gene transfer?
|
Viral vectors (most common) & non-viral
|
|
|
Advantages & disadvantages for viral vectors?
|
Advantages: effeciency, targeting specificity. Disadvantages: difficult to prepare, limit on size of gene, immunogenic
|
|
|
Charac of retrovirus as vector
|
23%. 7kb insert, used ex vivo. Advan: stable integration & efficient. Disadvan: infects dividing cells only & random integration
|
|
|
Charac of lentovirus as vector
|
0.8%. 7kb insert, HIV. Advan: No host immune response, stable integration. Disadvan: not widely used
|
|
|
Charac of herpesvirus as vector
|
3.2%. 150kb insert. Target neuronal cells. Advan: infects non-dividing cels, large genome. Disadvan: not widely used, possible expression latency
|
|
|
Charac of adenovirus as vector
|
25% Most commonly used, 30kb insert. Advan: easy to prepare, infects nondividing cells. Disadvan: doesn’t integrate into host genome, stim immune response.
|
|
|
Charac of Adeno-assoc virus as vector
|
4%. 4.5kb insert, stable integration, prefers chrom 19. Advan: stable integration & non-pathogenic. Disadvan: difficult to prepare & small genome
|
|
|
Charac of non-viral vectors?
|
naked DNA, liposomes, 26% of clinical trials
|
|
|
Advantages & disadvanages for non-viral vectors?
|
Advan: easy to prepare, not immunogenic, no limit on size of gene. Disadvan: lack of targeting specificity
|
|
|
Process to prepare vial vector?
|
Remove viral genes-> insert therapeutic gene w/ promoter & other reg of expression-> package & prolif in mamalian cell line-> purify viral vector-> treat patient
|
|
|
Disease symptoms & genetic of CFTR?
|
Most common fatal auto recessive disease in whites. Inc viscosity of secretions. Most common defect is 3 nucleotide deletion-> loss of single AA (delta508). Chrom 7
|
|
|
Status if CF gene therapy?
|
Normal copies of CFTR will correct CF cell in culture-> 1st gene therpay in humans-> 9 CF gene therapy centers-> 5 clinical trials (3 liposomes, 1 adenovirus, 1 AAV)-> 2 Phase II trials (AVV vectors improves ling fcn)
|
|
|
Future of CF gene therapy?
|
Modify therapy to prevent immune response, improve vectors, extend effects of treatment, & expand therapy to other organs
|
|
|
Types of hemophilia?
|
Hem A: x-linked, FVIII deficiency. Hem B: X-linked, FIX deficiency (most common)
|
|
|
Charac of hemophilia?
|
Uncontrollable bleeding & joint damage. Severe (<1% normal clottinf factor): Treated w/ wkly injections of blood proteins (expensive). Can get Hepatitis C or HIV. Moderate: 1-5% clotting, needs fewer injections
|
|
|
Status of hemophilia gene therapy?
|
FVII (A) & FIX (B) genes cloned. Successful in animals but FVIII I higher antigenic. Phase II & III trial for FIX (AAV)-> inc circ FIX & required fewer injects for 6mths
|
|
|
Future of hemophilia gene therapy?
|
Improve vectors, reduce immunogenic response (esp FVIII), determine best admin rout & target cell
|
|
|
Protocal types w/ most approved clinical trials?
|
Cancer, vascular disease (atherosclerosis), mongenic (CF, SCID), & infectious (HIV)
|
|
|
1st commercial gene therapy product?
|
Gendicine (2005)-AV serotype expresses p53-> treat head & neck squamous cell carcinoma
|
