Biologics

Question 1

What are biologics?

Answer 1

• Drugs that can be composed of complex combinations of sugars, proteins or nucleic acids.
• They may be living entities.
• Much larger than small molecule drugs.
• Cannot cross blood-brain barrier.

Question 2

What are the 6 mechanisms of action of biologics?

Answer 2

1. Ligand Blockade - antibody can bind to ligand, preventing it from binding to receptor.
2. Receptor Blockade - antibody binds to receptor - like competitive inhibition.
3. Receptor Downregulation - antibody binds to receptor, causing internalisation of receptor.
4. Signalling Induction - binds to receptor, causing cascade terminating in apoptosis.
5. Cell Depletion
6. Payload Delivery - Antibody delivers a killing mechanism - may have radioactive ligand, cytotoxin attached to it.

Question 3

What are the main classes of biologics?

Answer 3

• Monoclonal Antibodies
• Other proteins and polypeptides
• Viral and non-viral vectors
• Oligonucleotides
• Cells.

Question 4

Proteins and polypeptides have been modified to imporve therapeutic outcomes. What are examples of this?

Answer 4

Fast-acting insulin analogues - changing a couple of amino acids means it is less likely to bind to other insulin molecules - less likely to form aggregates, increased effectivity.

Long-acting insulin analogues - large fatty acid side chain added to insulin, more likely to been taken up into subcutaneous fat, slower release, longer lasting, less risk of hypoglycaemia.

Question 5

What is stable transfection and what are the issues with it?

Answer 5

Modified gene is incorpareted into the host’s genome.
Cannot control where gene is inserted, may result in activating onco-genes leading to cancer.

Question 6

What is transient transfection?

Answer 6

DNA / mRNA remains free in nucleus, not incorporated in genome. Genetic material not inherited by offspring.

Question 7

What features would the ideal vector for gene therapy have?

Answer 7

• High concentration
• Stable
• Can produce on large scale
• Control over expression and site of genome integration
• Not causing immune response.

Question 8

What is an example of a viral vector used in the treatment of retinal dystrophy? How does it work?

Answer 8

AAV Vector
Used in treatment of retinal dystrophy (arises from mutated gene). Fully functional version injected using AAV vector. Transient transfection - shown 3 years positive prognosis from 1 injection.

Question 9

What are the 2 categories of cells used as biologics?

Answer 9

• Autologous - come from the person, altered and returned to same person.
• Allogenic - cells from same species.