Lecture 5 - Genetics and Treatment Flashcards
decitabine is a DNA ______ agent used to help increase the levels of ____ in sickle cell anemia
hypomethylating;
HbF
what disorder is ivacftor/kalydec used to treat?
CF
helps improve FEV
____ ____ can be given to patietns with urea cycle disease to divert ammonia away
sodium benzoate
a ______ _____ can be given to patients with Duchenne’s to cause skipping of a stop codon in exon 51
antisense oligonucleotide
with viral gene therapy, a ______ sequence is required in addition to the therapeutic sequence
packaging
ie it has genes to make viral envelope
retrovrius vectors:
does gene get passed to progeny of cell?
requires ____ cells. risk of _____ mutagenesis
yes;
dividing;
insertional
adenovirus vectors:
does gene get passed to progeny of cell?
_____ ie may stimulate destruction of transgene containing cells
no (so transient expression);
immunogenic;
low risk of insertional mutagenesis, easy to purify and concentrate
Adenosine Deaminase Deficiency:
inheritance =
causes accumulation of ____ –> _____ toxicity and SCID
autosomal recessive;
dATP;
lymphocyte
ADA deficiency:
can treat with pegylated _____;
ie a ____cellular replacement for a ___cellular enzyme
ADA;
extracellular, intracellular
X-linked SCID:
due to defective ____;
can use ex vivo gene therapy with ____ + cells–> risk of developing ____
IL-2 Receptor (gamma chain);
CD34+
leukemia
factor 8 deficiency can be treated by injecting a vector into ____, which is a good target because the cells rarely divide
muscle
Ornithine Transcarbamylase (OTC) deficiency:
inheritance =
excess _____ _____ is converted to ____ ____
X-linked recessive;
carbamoyl phosphate, orotic acid;
OTC deficiency:
findings include increased _____ in blood and urine, decreased ____, and symptoms of hyper______
orotic acid;
BUN;
hyperammonemia
no anemia
jesse gelsinger:
had OTC, was given gene therapy contained in a _____ vector. died from strong ____ ____
adenovirus;
immune response
method to increase aggressive chemo:
introduce _____ gene into stem cells, which repairs DNA damage, treat patient with _____, which causes DNA damage (in cancer cells)
MGMT;
BCNU
2 ways to interfere with gene expression by affecting DNA
decoys, triplex formation
a _____ is RNA with enzymatic activity that can target RNA for degradation
ribozyme
miRNA:
coding or noncoding RNA?
act pretranscriptionally or post transcriptionally?
target the ____ region of specific mRNAs
noncoding;
post transcriptionally;
3’ untranslated region
miRNA:
binds to the ______ _____ complex –> repression of _____ or mRNA degradation
RNA-induced silencing complex (RiSC);
translation
siRNA:
enters cell by ____ _____.;
induces ____transcriptional gene silencing by binding complementary sequences
chemical transcfection;
post
shRNA:
is expressed in a cell from a ____, resulting in ____ similar to miRNA
vector;
hairpins
ie shRNA = miRNA except expressed as a vector
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
3, 1, 2
2 places you can get adult stem cells from
bone marrow; peripheral blood (via apheresis)
what location of the pre-implantation embryo can you get stem cells from?
inner cell mass
with somatic cell nuclear transfer/therapeutic cloning, an enucleated ______ receives the nucleus of an ____ cell
oocyte (egg);
adult
autologous cells are from ______;
allogenic cells are from ______
self (ie your own cells);
someone else (of same species)
