Therapeutic potential of regulatory RNAs 2 2.0 Flashcards
(32 cards)
What are locked nucleic acids?
Altered structures of DNA or RNA, not strictly DNA or RNA–> they are synthetic nucleic acids
Features of locked nucleic acids?
Oxygen present at the 2’ carbon which is crosslinked to carbon at position 4
Why are locked nucleic acids used?
Exonucleases and the immune system wont recognise them
Benefit of locked nucleic acids other than not being recognised?
They bind more potently to their targets than siRNAs do
How are siRNAs helped to cross the cell membrane?
They are encased in lipid nanoparticles
What types of lipids make up lipid nanoparticles?
Neutral lipids and cationic lipids
How is the -ve charge of siRNAs neutralised?
Cationic lipids are +vely charged
How is the molecular weight of siRNAs increased?
Polyethylene groups
Which two things to lipid nanoparticles do that helps siRNAs?
Remove the -ve charge and increase their molecular weight
When are lipid nanoparticles used?
When a systematic delivery is wanted
What type of delivery is used when you want to deliver siRNAs to a specific organ or cell type?
Targeted delivery
What encases siRNAs in targeted delivery?
Targeted cationic polymers
What make up targeted cationic polymers?
polycations, polyethylene groups, targeting ligand
What is the targeting ligand specific to in targeted delivery?
A receptor on the surface of the cell/organ you are aiming for
How is the polymer nanoparticle taken up in targeted delivery?
Receptor mediated endocytosis
Issues with receptor mediated endocytosis?
The molecules are not readily released from the endosome
What happens if the contents of an endosome is not readily released?
They get transferred to a lysosome where they are degraded
What is endosomal escape?
The release of something from an endosome
What is used to aid endosomal escape?
Using proton sponge groups
Where are proton sponge groups added?
siRNA complex
What do proton sponge groups do?
Cause protons to be pumped into the endosome, eventually causing it to burst
Examples of successful in vivo trials?
Haemophilia, ebola
What causes hemophilia?
mutations in clotting factors, so they are not produced–> persistent bleeding
Where are clotting factors produced and what with?
In the liver, with anticoagulants
