Gene Therapy Flashcards
Vector
System to deliver the genetic material into cells. Can be simple plasmid DNA, DNA (RNA) complexes, liposomes or nanoparticles. It is derived from viruses
Gene therapy
Addition of genetic material (DNA, coding mRNA, regulatory RNA) to cells or tissues
Ex vivo
Cells removed from body, incubated with a vector to introduce the new genetic material, and the modified cells returned. Good for the hematopoietic system
In vivo
- Localized delivery: use bronchoscope, vascular catheter, endoscope
- Systemic delivery: vector directly introduced into patient finds specific cells, either through bulk physical processes or by more specific engineering to target the vector to a certain cell type
Retroviral vectors
Advantage that they may integrate it into their genomes into the host genome, so allowing for long term persistence and gene expression
Lentiviral vectors
Subset of RVs, derived from HIV-1, which are especially good at delivering genes to cells of hematopoietic system
Adenoviral vectors
Not permanent, and can provoke a strong immune response, but this is good for some applications such as cancer
Adeno-associated viral vectors
Long lasting even though they can’t integrate into chromosome; non-immunogenic, different serotypes favor different tissues, so some targeting possible. Increasingly popular to treat diseases of muscle and eye
Primary immune deficiencies
The genetic absence of a protective immune system. Usually a fatal disease with infants dying from overwhelming infections.
X-linked SCID
Lack common gamma chain, defects in T, NK and B cells. Lethal by 4 months if untreated, survival 10 years under sterile conditions.
Leber’s congenital amaurosis
Inherited form of progressive blindness caused by defective RPE65 gene, involved in pathway sending signal to brain
Zinc finger nuclease
Linking fingers lengthen the DNA binding site. Adding a nuclease domain creates the ZNF. They bind to DNA and target sequence in pairs, and specifically cut the DNA at that site.
