Biologics Flashcards
What are oligonucleotides?
Short RNA/DNA molecules
Define biologics
An active pharmaceutical ingredient produced in living organisms that resonably cannot be synthesised by chemical means
Give some common therapeutic uses of biologics
- Vaccines
- Antibodies
- Replacement of a deficient/abnormal protein
- Enhancing/inhibiting processes
Give 5 types of biologics
- Monoclonal antibodies
- Other proteins + polypeptides
- Viral + non-viral vectors
- Oglionucleotides
- Cells
Why are monoclonal antibodies called ‘monoclonal’?
They are identical because they were produced by clones of the same cell
What are the 6 mechanisms of monoclonal antibodies?
- Ligand blockade
- Receptor blockade
- Receptor downregulation
- Signalling induction
- Cell depletion
- Payload delivery
In the context of monoclonal antibodies: what is receptor downregulation?
Binds to the receptor and induces internalisation which reduces the number of receptors avaliable
In the context on monoclonal antibodies: what is signalling induction?
MAbs induce signalling by coactivation of receptors, e.g. can cause programmed cell death
In the context on monoclonal antibodies: What is cell depletion?
MAbs tag cells (often tumour cells) to make it easier for the immune system to recognise a pathogenic cell
In the context on monoclonal antibodies: What is payload delivery?
Small (drug) molecules can be conjugated to the antibody in order to kill a cell which is tagged
Currently what type of diseases are treated using antibodies?
- auto-immune diseases
- inflammatory diseases
- cancer
Define immunogenicity
The ability of a substance to provoke an immune response
What are the advantages of monoclonal antibodies vs small molecules?
- High selectivity
- Longer lasting so administered less frequently
- Fewer side effects
- Bigger therapeutic window
- Neutralise disease causing molecules
What are the disadvantages of monoclonal antibodies vs small drugs?
- immunosuppression
- immunogenicity
- Limited targets
- limited to certain body compartments
- invasive route of administration
What are the 4 barriers for vector delivery?
- Genome persisitence (gene must be inserted genome)
- Transcriptional acitivity
- Immune response
- Uptake, uncoating, and transport of virus into cell
Give some advantages of recombinant human insulin vs insulin from pigs
- does not activate immune response
- safer
- faster acting
- longer lasting
Give a disadvantage of using viral vectors to treat disease
- Can cause unwanted alteration of gene expression
- Can cause cancer
How has insulin been engineered to last longer?
- Fatty acid chain added
- This interacts with the albumin in the blood
- This allows insulin to be ‘stored’ in the blood
What is transcient transfection?
When a viral vector delivers a gene into the nucleus but is not inserted into the genome
Give 2 methods of gene delivery into a patient
- Therapeutic gene is put into AAV and injected into the patient
- Cells removed from the patient are infected with edited virus and then re-introduced into the body
What does AAV stand for?
Adeno-associated virus
Give an example of a disease which has been treated using in vivo viral delivery
Retinal Dystrophy
Give an example of a viral vector which is used for transcient transfection
AVV
Give an example of a viral vector which is used for long term gene change
Retroviral vectors
