Gene Therapy
What does CAR in CAR-T cell therapy stand for?
Chimeric antigen receptor
What causes spinal muscular atropy?
loss of SMN protein
Give an example of a bio better.
PEG addition
What holds together the light and heavy chains of an antibody?
disulfide bonds
What drug binds to the 30S subunit and inhibits binding of aminoacyl-tRNAs (bacteria)?
Tetracycline
Give an example of ex vivo and and in vivid gene therapy.
Ex vivo: zynteglo
In vivo: luxturna and zolgensma
What is an example of a RNA gene therapy for hATTR amyloidisis?
Onpattro (Patisiran)
What do you lack with Pompe disease?
alpha-1,4-glucosidase
What do monoclonal antibodies recognize?
a single epitope on a single antigen
What drug prevents RNA elongation (prokaryotes and eukaryotes) from streptomcyes, a bacteria found in the soil?
Actinomycin
What makes gene therapy challenging?
the body and cells have aggressive defense mechanisms against any foreign DNA/RNA
What does dystrophin do and what happens if it's lost?
stabilizes muscle, causes muscle waisting
Give one reason as to why CHO cells are used in epoetin production?
-they grown in suspension
-they grow in defined media lacking animal serum
-they can perform complex post translational modifications
When is trastuzuman emtansine used in patient with HER2 breast cancer?
-if the pt received prior therapy for metastatic disease
-if the patient developed recurrence during or within six months of completing adjuvant therapy
What drugs is a a guanine nucleoside (lacking a cyclic sugar) that is selectively phosphorylated by viral thymidine kinases and selectively incorporated into DNA by viral DNA polymerases?
Acyclovir
How does CAR-T cell therapy work?
autologous T cells are harvested from blood, genetically modified, stimulated, and then reintroduced into the patient to attack the cancer
What is the MOA for Onpattor (Patisiran)
1. Patisiran binds to the TTR mRNA
2. Patisiran:TTR mRNA complex is recognized by RISC
3. TTR mRNA is cleared by RISC, preventing translation into protein
What are the biotech production steps of human proinsulin?
1. mRNA isolated from pancreatic islet cells
2. double stranded cDNA produced
3. cDNA ligated into bacterial plasmid
4. plasmid transfected into bacteria
5. bacteria produce proinsulin
Describe ADCC. (antibody dependent cell mediated cytotoxicity)
1. Mabs bind to tumor antigen
2. NK cells recognize the Fc region of Mabs via Fay receptors
3. NK cells cause tumor cell lysis
What drug remains inactive until it reaches the distal gut, where azoreductases encoded by the gut microbiome cleave the N‐N double bond to release active 5‐ASA?
Sulfasalazine
What are the steps of Zynteglo?
1. hematopoietic stem cells are isolated from pt and expanded in manufacturing facility
2. HSCs are infected with lentivirus vector expressing a functional beta-globin gene with a Thr-87-Gln switch
3. The beta globin protein pairs with alpha globin to produce functional hemoglobin
What is the MOA for Spinraza (Nusinersen)?
1. after spinal injection, nusinersen binds to the SMN2 primary transcript, prevents exon 7 from being spliced out
2. SMN2 mRNA containing exon 7 is translated into protein
3. SMN2 protein substitutes for missing SMN1 protein
What is the MOA of Novolog? What is the MOA of Lantus?
Novolog: asp replaces pro at position 28B
Lantus: Gly replaces San at position 21A
Describe Indirect and Sandwhich ELISA
Indirect: starts with an antigen coated well, then the specific antibody binds to the antigen and then the enzyme linked antibody binds to the specific antibody
Sandwich: starts with a monoclonal antibody coasted well then then antigen bonds to antibody and then a second monoclonal antibody, linked to enzyme, binds to immobilized antigen
This drug is used in combination therapy (with 5-FU) and leads to the toxic BUILDUP of 5‐FU due to inhibition of the 5‐FU catabolic enzyme dihydropyrimidine dehydrogenase (DPD) through irreversible binding by (E)‐5‐(2‐bromovinyl)uracil (BVU).
Sorivudine