Gene therapy Flashcards
Tell about the viral vectors used for gene therapy
Retrovirus Lentivirus Adeno associated virus Adenovirus Herpes simplex virus
Tell about the non-viral vectors used for gene therapy
Nude DNA
Lipoplexes
Polyplexes
What are the gene therapy which have reached the market
Gendicine Oncorine Glybera Imlygic Strimvelis
Tell about Gendicine
Adenovirus based.
Gendicine is a recombinant adenovirus engineered to express wildtype-p53 (rAd-p53).
Designed to treat patients with tumors which have mutated p53 genes.
What is this??? Recombinant adenovirus engineered to express wildtype-p53 (rAd-p53).
Gendicine
Tell about Glybera
Adenovirus based.
Glybera is a recombinant adenovirus engineered to express LPL enzyme. Designed to restore the LPL enzyme activity which is required to enable the processing, or clearance, of fat-carrying chylomicron particles formed in the intestine after a fat-containing meal.
Tell about Oncorine
Adenovirus based
Oncorine is a recombinant adenovirus engineered by deleting E1B-55KD and E3 region of wild adenovirus type 5. E1B-55KD is involved in the degradation of P53. So in normal cells in which P53 will normally be functioning, p53 will have an upper hand and the virus cant harm. But in tumour cells in which the p53 will not be functioning, the virus will proliferate freely and the proliferation of virus will destroy the cancerous cells.
Tell about Imlygic
Herpes simplex virus -1 based
Imlygic is a recombinant herpesvirus that has been genetically modified to replicate within tumors and produce the immune stimulatory protein (granulocyte-macrophages colony-stimulating factor (GM-CSF)). On being injected into melanoma tumors, it causes lysis of tumor cells followed by release of tumor-derived antigens. The derived tumour antigen stimulate the immune system against the tumour. Along with this, the virally derived GM-CSF also promote an antitumor immune response. Still, the exact mechanism of action of this drug is unknown
Tell about Strimvelis
Retrovirus based
First ex vivo stem cell gene therapy.
Strimvelis is a recombinant retrovirus which is engineered to express Adenosine deaminase complementary DNA (cDNA). The gene therapy IS targeted against the Adenosine deaminase (ADA) deficiency which is seen in SCID.
Tell about Chimer antigenic receptor based immunotherapy
Autologous CD8+ T cells which are engineered to recognize and kill cells bearing tumor-specific antigens through a CAR(Chimeric antigen receptors). The Chimer antigenic receptor based immunotherapy combines the specificity of a monoclonal antibody with the proliferative and cytotoxic abilities of an activated CD8+ T cell.
Do you remember the story of Jesse Gelsinger case
OTC deficient patient
Fomivirsen describe?
Indicated for cytomegalovirus retinitis in HIV patients
It blocks translation of viral mRNA by binding to the complementary sequence of the mRNA transcribed from the template segment of a key CMV gene UL123, which encodes the CMV protein IE2.
Pegaptanib describe?
Indicated for wet macular degeneration of the retina.
It is a pegylated anti-vascular endothelial growth factor (VEGF) aptamer (a single strand of nucleic acid) that binds specifically to VEGF. VEGF plays a critical role in angiogenesis and permeability (increases permeability). These two are the primary pathological processes responsible for the vision loss associated with neovascular AMD.
It works as an antagonist to VEGF. When it is injected into the eye, it blocks the actions of VEGF. This in turn leads to the reduction in the growth of the blood vessels located within the eye. This ultimately results in
control the leakage and swelling within the eye.
Mipomersen describe?
Indicated for familial hypercholesterolemia
It binds to the messenger RNA coding for apolipoprotein B-100 (ApoB-100). Apo B 100 is the main component of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). The untranslated mRNA will be degraded by the enzyme ribonuclease H. translated
Eteplirsen describe?
Indicated for Duchenne muscular dystrophy
It is a morpholino antisense oligomer which triggers excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin. The eteplirsen when given to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional (although modified by having an internal deletion consisting of both the patient’s original defect, as well as the therapeutically skipped exon) dystrophin.
