4: Gene and Cell Based Tx Flashcards
describe gene therapy
The introduction, removal, or change in the content of a person’s genetic code with the goal of tx or curing a disease
transferred genetic material in gene therapy changes how
single protein/ group of proteins are produced by the cell
Gene therapy can be used to
1. reduce levels of a disease causing version of a protein
2. increase production of a disease fighting protein
3. to produce new/ modified proteins
4. all of the above
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what is cell therapy
Transfer of intact, live cells into a patient to help lessen or cure a disease
cells that originate from a patient are __________ and from a donor are ______
autologous
allogenic
_________ cells can transform into any cell type
pluripotent
________ cells can transform into a few cell types
multipotent
______ cells are fixed in type
differentiated or primary
genetic alteration can lead to
dysfunctional protein = disorder
_______ drugs provide temporary or symptomatic management
conventional small molecule/ chemical drugs
___ drugs are costly and difficult to produce
protein drugs
which drugs exhibit less desirable PK properties + can cause life threatening toxicities
proteins
which of the following is not a quality of gene therapy
1. one time treatment
2. long lasting production of therapeutic protein
3. localized to target tissue
4. can be taken as PO pill
5. minimal toxicity
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changes to ___ line cells are inheritable
germ line
describe augmentation gene therapy
Maintain long term expression of proteins associated with transferred (wild type) gene by providing a functional copy without deleting the dysfunctional gene
Maintain long term expression of proteins associated with transferred (wild type) gene by providing a functional copy without deleting the dysfunctional gene describes ____ gene therapy
augmentation
describe gene suppression
Suppress expression of a mutated, harmful gene or accumulation of dysfunctional protein using RNA interference
gene suppression is the suppression of the expression of a mutated, harmful gene or accumulation of dysfunctional protein using _______ interference
RNA
what is used to to correct a mutated sequences by generating a DNA break, then rejoining via homologous template or nonhomologous nucleotide editing
genome editing
leber’s congenital amaurosis is a
autoimmune recessive retinal pigment epithelial 65 kDA protein (RPE65) genetic mutation = loss of production of retinoid isomerohydrolase (nonfunctional protein we want to introduce), responsible for visual cycle
treatment for leber’s congenital amaurosis is
Voretigene Naparvovec
what is Voretigene Naparvovec
genetically altered, nonreplicating adeno associated virus (AAV) carrying the functional human RPE65 gene = gene augmentation therapy
Voretigene Naparvovec is an example of
gene augmentation therapy
AAV are ________ viruses
small single stranded
benefits of AAV include
nonpathogenic, nonreplicating, non integrating, ability to transduce nondividing cells, low immunogenicity
VN route
subretinally into each eye on separate days + perioperative prednisone
AAV vector carrying RPE65 binds to cell surface receptor → AAV vector gets _______________→ either proteosome mediated degradation OR ________________________ → uncoating in nucleus and release of single stranded AAV genome (as a stabilized extragenic episome and lacks integration into the host genome → conversion to ________________ → transcription into mRNA → translation and production of RPE65 protein constitutively
endocytosed via endosomes
gains entry into nucleus
double stranded DNA
T or F: there is little evidence of immunogenicity for VN
T- likely due to ocular immune privilege
VN AEs include
ophthalmic issues, conjunctival hyperemia, cataracts, IOP elevation
- mostly related to concomitant steroid therapy
T or F: AAV incorporates itself into host genome for constitutive translation and production of RPE protein
F
AAV genome is stored as a
stabilized extragenic episome
