Biopharmaceuticals and gene therapy

Question 1

what is biopharmaceuticals?

Answer 1

A biological molecule used as a pharmaceutical.

can either be protein or oligonucleotide in nature

Question 2

what is first generation biopharmaceuticals?

Answer 2

biological molecules in its endogenous form.
They have not been modified.
For example human insulin and Human growth hormone

Question 3

what is second generation biopharmaceutical?

Answer 3

Biological molecules that have undergone modification therefore altering the nature of the product.

Question 4

what production method is used in biopharmaceuticals?

Answer 4

bacterial expression system:

human gene is combined with bacterial plasmid to form a recombinant plasmid.

bacterial transformation results in heterologous expression.

protein purification the takes pace.

Question 5

what is the advantage of this production method?

Answer 5

high yield end product

Question 6

what are the disadvantages of this method?

Answer 6

may contain endotoxins

post-translational processing may differ compared to mammalian cells

Question 7

what are alternative expression systems?

Answer 7

transgenic cattle
plant: tobacco/edible plants
Chinese hamster ovary cells

Question 8

what is the advantage of using transgenic cattle and plants for alternative expression systems?

Answer 8

genes can be put into tobacco more easily = quicker and efficient

transgenic cattle produce milk with proteins that utilise production of proteins

Question 9

what are some problems with first generation mAbs?

Answer 9

can provoke an immune response
short half-life
also can’t activate human complements

Question 10

how can the lack of activation of human complements be addressed?

Answer 10

By humanising the antibodies (forming a chimera)
A mix between human and mice
effective therapeutics can be achieved from this due to the specificity formed.

Question 11

what is an alternative approach to delivering entire genes?

Answer 11

using oligonucleotides

short antisense oligonucleolotides specifically

Question 12

what is mipomersen used for?

Answer 12

to treat hypercholesterolaemia

Question 13

what is the comparison in size between conventional drugs and biopharmaceuticals?

Answer 13

biopharmaceuticals are larger in size compared to conventional drugs

Question 14

what is the comparison in synthesis between conventional drugs and biopharmaceuticals?

Answer 14

conventional drugs are easier to synthesise in identical batches

Question 15

what is the relationship between dose and effect for conventional drugs and biopharmaceuticals?

Answer 15

conventional drugs have a more predictable relationship between dose and effect whereas biopharmaceuticals are less predictable

Question 16

what is gene therapy?

Answer 16

a strategy used to deliver a functioning copy of a defective gene to a target cell by using a suitable vector.

Question 17

give an example of second generation biopharmaceuticals?

Answer 17

insulin synthesised to have a longer duration of action

Question 18

what is an advantage of biopharmaceuticals over conventional drugs?

Answer 18

biopharmaceuticals have a lower incidence of adverse effects

Question 19

how does an antisense oligonucleotide bring about its therapeutic effect?

Answer 19

by blocking the translation of mRNA once it has reached the ribosome

Question 20

give some example of the therapeutic applications of gene therapy:

Answer 20

gendicine: treatment of replacing faulty P53 protein causing head and neck cancer
glybera: Aden-associated virus construct
strimvelis: ex-vivo therapy to reat SCID