biological and gene therapy

Question 1

what is biological products?

Answer 1

Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting-edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available

Question 2

what is biopharmaceuticals?

Answer 2

Biopharmaceuticals include proteins, antibodies (and oligonucleotides) used as drugs.

First-generation biopharmaceuticals are mainly copies of endogenous proteins or antibodies, produced by recombinant DNA technology.
Second-generation biopharmaceuticals ‘engineered’ to improve the performance of the protein or antibody.

Question 3

what are the considerations need to be taken about design and use of a biological?

Answer 3

Potency
Specificity
Side effects
Delivery

Can’t be delivered orally (esp. if peptide/protein)
Can’t/difficult to cross the blood brain barrier
May require surgery
Broken down by ubiquitous proteases
Even if injected rapidly metabolized

Manufacture
Cost more to make than organic chemicals
Yields may be low
Purification
Quality control

Stability
Proteins often unstable
Sensitive to heat, light, etc
Storage/shelf life an issue

Question 4

what is insulin and what does it do?

Answer 4

Insulin (Hormone)

Replaces insulin in type I diabetics who have reduced ability to produce insulin

Question 5

what is somatotropin and what does it do?

Answer 5

Somatotropin (Hormone)

Growth hormone to prevent reduced stature.

Question 6

what is Factor VIII and what does it do

Answer 6

(Coagulation Factor)

For haemophilia replaces a missing clotting factor in the blood.

Question 7

moA of insulin

Answer 7

Indication: Type I diabetes mellitus

Mechanism of action: Insulin receptor agonist

Increases glucose uptake, decreases glucose formation, increases glucose use

Insulin is generally administered by subcutaneous injections. Injection devices (pens) are usually the most convenient way for patients to self-administer a dose

Lots of different types of insulin are available. Short-acting and long-acting. Long acting forms are modified to increase half-life.

Question 8

give examples of growth factors and their use?

Answer 8

Erythropoetin
EPO stimulates the production of red blood cells in treatment of chronic renal failure and anaemia associated with EPO deficiency.

Platelet-derived growth factor
PDGF wound healing

Bone morphogenic proteins
BMP2 orthopaedic surgery, promote bone repair
BMP7 promotes vertebral fusion

Interferons
IFNa hepatitis
IFNb multiple sclerosis

Question 9

what is Tissue Plasminogen Activator (tPA) and its use?\

Answer 9

coverts plasminogen to plasmin
converts thrombus blood clot to proteolytic degradation product
tPA is a serine protease enzyme acts as a “clotbuster”
Administered within 3 hours of stroke onset improves clinical outcome (death, disability) at 3 months (2002).

Question 10

what does alteplase do?

Answer 10

• tissue plasminogen activator
• activates production of plasmin from its precursor plasminogen
• plasmin is an enzyme that degrades fibrin clots
• used in acute ischemic stroke

Question 10

what does alteplase do?

Answer 10

• tissue plasminogen activator
• activates production of plasmin from its precursor plasminogen
• plasmin is an enzyme that degrades fibrin clots
• used in acute ischemic stroke

Question 11

what is Monoclonal antibodies

Answer 11

Very specific antagonists
Bind to natural ligand
Neutralise effect
May contain part of receptor

Humanised antibodies
Overcome immune response

Also known as disease modifying agents

Question 12

what is nanobodies

Answer 12

Used to develop treatments for ‘difficult’ targets

ion channels

Question 13

what is gene therapy?

Answer 13

Replacement of a defective gene(s) with a normal, healthy gene(s).

Broader definition: “……. represents an opportunity for the treatment of genetic disorders in adults and children by genetic modification of human body cells ……”

Question 14

what are the different types of gene therapy?

Answer 14

Germline (sperm/egg)
Possible permanent cure
Huge ethical concerns!
E.g. IQ, hair/eye/ skin colour

Somatic cell (diploid)
Targeting only cells that live as long as the individual (one individual, one generation)
Make up all approved gene therapy trails in humans

Question 15

what are vectors delivery system?

Answer 15

Retroviral - 8000 base pairs (RNA)
Adenoviral -7500 base pairs (DNA)
Adeno-associated viral - 500 base pairs (DNA)

Non-viral
Naked DNA
Polymers/liposomes
Nanoparticles
Gene “gun”

Question 16

what were set backs in gene therapy?

Answer 16

Adenovirus vector.
Jesse Gelsinger died extreme immune reaction to vector resulted multiple organ failure.
All trials stopped.
Subsequent FDA investigation found flaws in the trial set up.

Ornithine Transcarbamoylase deficiency