Lecture 5 - Genetics and Treatment

Question 1

decitabine is a DNA ______ agent used to help increase the levels of ____ in sickle cell anemia

Answer 1

hypomethylating;

HbF

Question 2

what disorder is ivacftor/kalydec used to treat?

Answer 2

CF

helps improve FEV

Question 3

____ ____ can be given to patietns with urea cycle disease to divert ammonia away

Answer 3

sodium benzoate

Question 4

a ______ _____ can be given to patients with Duchenne’s to cause skipping of a stop codon in exon 51

Answer 4

antisense oligonucleotide

Question 5

with viral gene therapy, a ______ sequence is required in addition to the therapeutic sequence

Answer 5

packaging

ie it has genes to make viral envelope

Question 6

retrovrius vectors:
does gene get passed to progeny of cell?

requires ____ cells. risk of _____ mutagenesis

Answer 6

yes;
dividing;

insertional

Question 7

adenovirus vectors:

does gene get passed to progeny of cell?

_____ ie may stimulate destruction of transgene containing cells

Answer 7

no (so transient expression);

immunogenic;

low risk of insertional mutagenesis, easy to purify and concentrate

Question 8

Adenosine Deaminase Deficiency:
inheritance =
causes accumulation of ____ –> _____ toxicity and SCID

Answer 8

autosomal recessive;
dATP;
lymphocyte

Question 9

ADA deficiency:
can treat with pegylated _____;
ie a ____cellular replacement for a ___cellular enzyme

Answer 9

ADA;

extracellular, intracellular

Question 10

X-linked SCID:
due to defective ____;

can use ex vivo gene therapy with ____ + cells–> risk of developing ____

Answer 10

IL-2 Receptor (gamma chain);

CD34+

leukemia

Question 11

factor 8 deficiency can be treated by injecting a vector into ____, which is a good target because the cells rarely divide

Answer 11

muscle

Question 12

Ornithine Transcarbamylase (OTC) deficiency:
inheritance =
excess _____ _____ is converted to ____ ____

Answer 12

X-linked recessive;

carbamoyl phosphate, orotic acid;

Question 13

OTC deficiency:

findings include increased _____ in blood and urine, decreased ____, and symptoms of hyper______

Answer 13

orotic acid;
BUN;
hyperammonemia

no anemia

Question 14

jesse gelsinger:

had OTC, was given gene therapy contained in a _____ vector. died from strong ____ ____

Answer 14

adenovirus;

immune response

Question 15

method to increase aggressive chemo:

introduce _____ gene into stem cells, which repairs DNA damage, treat patient with _____, which causes DNA damage (in cancer cells)

Answer 15

MGMT;

BCNU

Question 16

2 ways to interfere with gene expression by affecting DNA

Answer 16

decoys, triplex formation

Question 17

a _____ is RNA with enzymatic activity that can target RNA for degradation

Answer 17

ribozyme

Question 18

miRNA:
coding or noncoding RNA?

act pretranscriptionally or post transcriptionally?

target the ____ region of specific mRNAs

Answer 18

noncoding;

post transcriptionally;

3’ untranslated region

Question 19

miRNA:

binds to the ______ _____ complex –> repression of _____ or mRNA degradation

Answer 19

RNA-induced silencing complex (RiSC);

translation

Question 20

siRNA:
enters cell by ____ _____.;
induces ____transcriptional gene silencing by binding complementary sequences

Answer 20

chemical transcfection;

post

Question 21

shRNA:

is expressed in a cell from a ____, resulting in ____ similar to miRNA

Answer 21

vector;
hairpins

ie shRNA = miRNA except expressed as a vector

Question 22

clinical trials:
phase ____ compares the new treatment to the current standard of care.

phase ____ assess safety and toxicity in healthy volunteers

phase ____ assess treatment efficacy and optimal dosing

Answer 22

3, 1, 2

Question 23

2 places you can get adult stem cells from

Answer 23

bone marrow;
peripheral blood (via apheresis)

Question 24

what location of the pre-implantation embryo can you get stem cells from?

Answer 24

inner cell mass

Question 25

with somatic cell nuclear transfer/therapeutic cloning, an enucleated ______ receives the nucleus of an ____ cell

Answer 25

oocyte (egg);

adult

Question 26

autologous cells are from ______;

allogenic cells are from ______

Answer 26

self (ie your own cells);

someone else (of same species)