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Mechanisms of Drug Action > Biologics > Flashcards

Biologics Flashcards

1
Q

What are oligonucleotides?

A

Short RNA/DNA molecules

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2
Q

Define biologics

A

An active pharmaceutical ingredient produced in living organisms that resonably cannot be synthesised by chemical means

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3
Q

Give some common therapeutic uses of biologics

A
  • Vaccines
  • Antibodies
  • Replacement of a deficient/abnormal protein
  • Enhancing/inhibiting processes
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4
Q

Give 5 types of biologics

A
  • Monoclonal antibodies
  • Other proteins + polypeptides
  • Viral + non-viral vectors
  • Oglionucleotides
  • Cells
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5
Q

Why are monoclonal antibodies called ‘monoclonal’?

A

They are identical because they were produced by clones of the same cell

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6
Q

What are the 6 mechanisms of monoclonal antibodies?

A
  • Ligand blockade
  • Receptor blockade
  • Receptor downregulation
  • Signalling induction
  • Cell depletion
  • Payload delivery
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7
Q

In the context of monoclonal antibodies: what is receptor downregulation?

A

Binds to the receptor and induces internalisation which reduces the number of receptors avaliable

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8
Q

In the context on monoclonal antibodies: what is signalling induction?

A

MAbs induce signalling by coactivation of receptors, e.g. can cause programmed cell death

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9
Q

In the context on monoclonal antibodies: What is cell depletion?

A

MAbs tag cells (often tumour cells) to make it easier for the immune system to recognise a pathogenic cell

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10
Q

In the context on monoclonal antibodies: What is payload delivery?

A

Small (drug) molecules can be conjugated to the antibody in order to kill a cell which is tagged

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11
Q

Currently what type of diseases are treated using antibodies?

A
  • auto-immune diseases
  • inflammatory diseases
  • cancer
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12
Q

Define immunogenicity

A

The ability of a substance to provoke an immune response

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13
Q

What are the advantages of monoclonal antibodies vs small molecules?

A
  • High selectivity
  • Longer lasting so administered less frequently
  • Fewer side effects
  • Bigger therapeutic window
  • Neutralise disease causing molecules
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14
Q

What are the disadvantages of monoclonal antibodies vs small drugs?

A
  • immunosuppression
  • immunogenicity
  • Limited targets
  • limited to certain body compartments
  • invasive route of administration
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15
Q

What are the 4 barriers for vector delivery?

A
  • Genome persisitence (gene must be inserted genome)
  • Transcriptional acitivity
  • Immune response
  • Uptake, uncoating, and transport of virus into cell
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16
Q

Give some advantages of recombinant human insulin vs insulin from pigs

A
  • does not activate immune response
  • safer
  • faster acting
  • longer lasting
17
Q

Give a disadvantage of using viral vectors to treat disease

A
  • Can cause unwanted alteration of gene expression
  • Can cause cancer
18
Q

How has insulin been engineered to last longer?

A
  • Fatty acid chain added
  • This interacts with the albumin in the blood
  • This allows insulin to be ‘stored’ in the blood
19
Q

What is transcient transfection?

A

When a viral vector delivers a gene into the nucleus but is not inserted into the genome

20
Q

Give 2 methods of gene delivery into a patient

A
  1. Therapeutic gene is put into AAV and injected into the patient
  2. Cells removed from the patient are infected with edited virus and then re-introduced into the body
21
Q

What does AAV stand for?

A

Adeno-associated virus

22
Q

Give an example of a disease which has been treated using in vivo viral delivery

A

Retinal Dystrophy

23
Q

Give an example of a viral vector which is used for transcient transfection

A

AVV

24
Q

Give an example of a viral vector which is used for long term gene change

A

Retroviral vectors

25
Q

Outline how genes can be delivered ex vivo using chimeric antigen receptor T-cells in treat leukemia

A
  • WBC are removed and infected with a virus
  • Virus inserts a gene for a receptor which can be recognised by the immune system
  • WBC are then reinjected, allowing the immune system to recognise and kill cancer cells
26
Q

Give 4 types of cells which are used therapeutically

A
  • Blood
  • Embyronic stem cells
  • Induced pluripotent stem cells
  • Genetically modified cells
27
Q

How can antisense oligonucleotides be used to treat disease?

A
  • Oligonucleotides are complementary to gene or part of gene
  • This suppresses expression of harmful gene
  • So less harmful protein produced

Mechanisms of Drug Action (8 decks)

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