4: Gene and Cell Based Tx

Question 1

describe gene therapy

Answer 1

The introduction, removal, or change in the content of a person’s genetic code with the goal of tx or curing a disease

Question 2

transferred genetic material in gene therapy changes how

Answer 2

single protein/ group of proteins are produced by the cell

Question 3

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

Answer 3

4

Question 4

what is cell therapy

Answer 4

Transfer of intact, live cells into a patient to help lessen or cure a disease

Question 5

cells that originate from a patient are __________ and from a donor are ______

Answer 5

autologous
allogenic

Question 6

_________ cells can transform into any cell type

Answer 6

pluripotent

Question 7

________ cells can transform into a few cell types

Answer 7

multipotent

Question 8

______ cells are fixed in type

Answer 8

differentiated or primary

Question 9

genetic alteration can lead to

Answer 9

dysfunctional protein = disorder

Question 10

_______ drugs provide temporary or symptomatic management

Answer 10

conventional small molecule/ chemical drugs

Question 11

___ drugs are costly and difficult to produce

Answer 11

protein drugs

Question 12

which drugs exhibit less desirable PK properties + can cause life threatening toxicities

Answer 12

proteins

Question 13

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

Answer 13

4

Question 14

changes to ___ line cells are inheritable

Answer 14

germ line

Question 15

describe augmentation gene therapy

Answer 15

Maintain long term expression of proteins associated with transferred (wild type) gene by providing a functional copy without deleting the dysfunctional gene

Question 16

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

Answer 16

augmentation

Question 17

describe gene suppression

Answer 17

Suppress expression of a mutated, harmful gene or accumulation of dysfunctional protein using RNA interference

Question 18

gene suppression is the suppression of the expression of a mutated, harmful gene or accumulation of dysfunctional protein using _______ interference

Answer 18

RNA

Question 19

what is used to to correct a mutated sequences by generating a DNA break, then rejoining via homologous template or nonhomologous nucleotide editing

Answer 19

genome editing

Question 20

leber’s congenital amaurosis is a

Answer 20

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

Question 21

treatment for leber’s congenital amaurosis is

Answer 21

Voretigene Naparvovec

Question 22

what is Voretigene Naparvovec

Answer 22

genetically altered, nonreplicating adeno associated virus (AAV) carrying the functional human RPE65 gene = gene augmentation therapy

Question 23

Voretigene Naparvovec is an example of

Answer 23

gene augmentation therapy

Question 24

AAV are ________ viruses

Answer 24

small single stranded

Question 25

benefits of AAV include

Answer 25

nonpathogenic, nonreplicating, non integrating, ability to transduce nondividing cells, low immunogenicity

Question 26

VN route

Answer 26

subretinally into each eye on separate days + perioperative prednisone

Question 27

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

Answer 27

endocytosed via endosomes
gains entry into nucleus
double stranded DNA

Question 28

T or F: there is little evidence of immunogenicity for VN

Answer 28

T- likely due to ocular immune privilege

Question 29

VN AEs include

Answer 29

ophthalmic issues, conjunctival hyperemia, cataracts, IOP elevation
- mostly related to concomitant steroid therapy

Question 30

T or F: AAV incorporates itself into host genome for constitutive translation and production of RPE protein

Answer 30

F

Question 31

AAV genome is stored as a

Answer 31

stabilized extragenic episome