Biologicals 3 Flashcards
What was Macugen?
The first aptamer drug and first RNA drug
What was Macugen used for?
Treatment of ‘wet’ age related macular degeneration
How does Macugen work?
Binds to VEGF, reducing blood vessel growth.
How is Macugen given?
IV injection every 6 weeks
What can RNAi do?
Knock down gene expression if sequence is known
What is miRNA derived from?
Genes that specifically code miRNAs
What can happen to cells with missing miRNAs?
DNA coding missing miRNAs could be delivered to cells to replace the missing miRNAs
Overexpressed miRNAs can be inhibited by what?
anti-miRNAs, complementary nucleotides that bind to the problem miRNA
What are vital in the boody’s defence against tumours?
Cytotoxic T lymphocytes
What to CTLs recognise?
Short antigenic peptides in association with major histocompatibility complex molecules displayed on the cell surface
Bone marrow derived dendritic cells display what to immature CTLs to activate them?
MHC-peptide complexes
What are the 4 main genetic therapy targets?
Cancer
Cardiovascular disease
Monogenic disease
Infectious diseases
What are the challenges to delivery of genetic material?
- Complex formation
- Transport from delivery site
- Cellular uptake
- Endosome release
- Trafficking
- Nuclear entry
- Transcription
- mRNA export
- Translocation
What can retroviruses be used to target?
Specific cells
What is the risk of using retroviruses?
Tumour development
Are adenoviruses ds or ssDNA?
dsDNA
Are retroviruses ssRNA or dsDNA?
ssRNA
Adenovirus infects divinding or non-dividing cells?
Both
What was Glybera approved for?
Treatment of lipoprotein lipase deficiency
What are the advantages of viral vectors?
High transfer efficiency
Some inherent tissue tropisms
What are the disadvantages of viral vectors?
Limited DNA/RNA capacity.
Difficult production.
What physical techniques can be used to create non-viral nucleic acid delivery?
Direct injection
Gene gun
Ultrasound
Electroporation
What chemical techniques can be used to create non-viral nucleic acid delivery?
Encapsulation
Complexation
What are the advanatges of non-viral vectors?
Easy to prepare and modify.
Reduced immunogenicity.
Large capacity
