genomics final drugs / diagnostics

Zynteglo

gene therapy for beta-thalassemia

- ex vivo: take hematopoietic stem cells from pt and infect with function beta-globin gene

- requires myleoablative conditioning

Luxterna

gene therapy for RPE65 mutation induced eye problems

- recombinant of serotype 2

Zolgensma

gene therapy for spinal muscular atrophy

- AAV9 virus modified with SMN complementary DNA

Kympriah, Yescarta, Tecartus

chimeric-antigen receptor - T cell therapy for cancer

- T cells harvested from pt and modified to attack their cancer

Onpattro

antisense oligonucleotide for hATTR amyloidosis

- binds to TTR mRNA to form a complex that gets degraded by RISC

- select C and U bases have 2'-O-(2-methyl) nucleosides

- uptake into hepatocytes via lipid nanoparticles binding to ApOE

- release via pH change

Spinraza

antisense oligonucleotide for spinal muscular dystrophy

- has 2'-O-(2-methoxyethyl) nucleosides and thioate linkages

- binds to SMN2 primary transcript to prevent exon 7 splicing

Exondys

antisense oligonucleotide for duchenne muscular dystrophy

- binds to dystrophin primary transcript to splice out exon 51 stop codon

- formation of short, but functional dystrophin

Novolog

rapid acting insulin hormone therapy

- pro to asp amino acid change on B chain to decrease oligomerization -> act faster

Lantus

long acting insulin hormone therapy

- asn to gly amino acid change on A chain and 2 extra arg on B chain to decrease solubility -> slower release

Epogen, Procrit

erythropoietin hormone therapy for kidney failure associated anemia

- produced using CHO cells bc they can preform glycosylation

Filgrastim, Pegfilgrastim

granulocyte colony stimulating factor for neutropenia

- Filgrastim: dosed daily

-Pegfligrastim: PEG addition increases half-life -> dosed once every chemo cycle

Myozyme, Lumizyme

1st generation alpha-1,4-glucosidase enzyme replacement therapy for pompe disease

- requires treatment to remove terminal sugars and epose mannose

- low mannose density

Nexviazyme

2nd generation alpha-1,4-glucosidase enzyme replacement therapy for pompe disease

- mannoses added

- "postproducton glycoengineering"

Pombiliti

3rd generation alpha-1,4-glucosidase enzyme replacement therapy for pompe disease

- CHO cells are engineer with golgi-mannosidase to increase mannose density

- "post-translational glycoengineering"

Opfolda

glucose analog

- used in addition to Pombiliti therapy for pompe disease to decrease Pombiliti's inactivation

Indirect Enzyme-Lined Immunosorbent Assay (ELISA)

diagnostic antibody test to detect if pt has specific antibodies

- antigen fixed in well -> add sample with primary antibody -> add secondary antibody with enzyme attached

Sandwich Enzyme-Lined Immunosorbent Assay (ELISA)

diagnostic antibody test to detect if pt has a specific antigen

- primary antibody fixed in well -> add sample with antigen -> add secondary antibody with enzyme attached

hCG urine test

diagnostic antibody test to detect if pt is pregnant

- reaction zone: contains primary antibody with enzyme attached; binds to hCG

- test zone: contains fixed secondary antibody that 'sandwiches' the hCG antibody complex + dye that reacts with enzyme

- control zone: captures leftover antibodies to ensure test in functioning correctly

HER2 immunohistochemistry

diagnostic antibody test to detect if pt had HER2 breast cancer

- more brown = more antigen

- determines course of treatment

Cimzia

monoclonal antibody for autoimmune conditions

- binds directly for TNF-alpha to block its proinflammatory signaling

- 'humanized' + 2 PEG groups

- no traditional Fc region to prevent ADCC

Zaltrap

monoclonal antibody for metastatic colorectal cancer with VEGF overexpression

- antibody with VEGF receptor fused to Fc region to trap VEGF

Eylea

monoclonal antibody for neoveascular macular degeneration

- antibody with VEGF receptor fused to Fc region to trap VEGF

Herceptin

monoclonal antibody for HER2+ breast cancer

- targets the base of the extracellular domain

Perjeta

monoclonal antibody for HER2+ breast cancer

- targets the dimerization arm of HER2

- can be used in combo with Herceptin to target multiple domains

Kadcyla

monoclonal antibody-drug conjugate for HER2+ breast cancer

- Herceptin + emtansine (antimiotic)

- covalent MCC linker bind emtansine to the lysines of Herceptin's Fc region

- used in Herceptin resistant tumors - when Herceptin is degraded, the emtasnine is released

Keyturda + Opidvo

monoclonal antibody-drug conjugate for PD-1 overexpressive cancer

- blocks PD-L1 from binding to PD-1 to relieve the inhibition of T cells

Primaquine

antimalarial

- genetic linked drug senesitivity: hemolytic reactions have higher incidence in dark-skinned races

- glucose 6-phosphate deficiency: abnormality that induces sensitivity and malarial resistance

Rifampicin

antibiotic for TB by preventing initiation via blocking RNA/DNA hybrid

Streptomycin

antibacterial

- inhibit initiation and cause misreading of mRNA

Tetracycline

antibacterial

- binds to the 30s subunit and inhibits the binding of aminoacyl-tRNAs

Chlorampenicol

antibacterial

- inhibits the peptidyl transferase activity of the 50s subunit 

Erythromycin

antibacterial

-  bind to the 50s subunit and inhibits translocation

Cisplatin

chemotherapy agent

- results in interstrand crosslinks

Warfarin

anticoagulant

- low-dose haplotype A - Asian (more T)

- high-dose haplotype B - African (more C)

- US: genotype-guided dosing did not improve anticoagulation control; more racial heterogeneity

- EU: genotype-guided dosing did improve anticoagulation control; less racial heterogeneity

- ancestry-informed genotype-guided strategies: improve efficacy and limit warfarin toxicity

Nortiptyline

tricyclic antidepressant

-prodrug

Sulfasalazine

anti-inflammatory

- normally activated by microbiome

- antibiotics: kill bacteria that activate -> decreased concentrations in the blood

Sorivuidine and Fluorouracil

cannot be used together

- 5-FU metabolism enzyme (DPD) is blocked by sorivuidine metabolite (BVU) causing a toxic 5-FU buildup 

- antibiotics: can alleviate buildup