Biopharmaceuticals and gene therapy Flashcards
what is biopharmaceuticals?
A biological molecule used as a pharmaceutical.
can either be protein or oligonucleotide in nature
what is first generation biopharmaceuticals?
biological molecules in its endogenous form.
They have not been modified.
For example human insulin and Human growth hormone
what is second generation biopharmaceutical?
Biological molecules that have undergone modification therefore altering the nature of the product.
what production method is used in biopharmaceuticals?
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.
what is the advantage of this production method?
high yield end product
what are the disadvantages of this method?
may contain endotoxins
post-translational processing may differ compared to mammalian cells
what are alternative expression systems?
transgenic cattle
plant: tobacco/edible plants
Chinese hamster ovary cells
what is the advantage of using transgenic cattle and plants for alternative expression systems?
genes can be put into tobacco more easily = quicker and efficient
transgenic cattle produce milk with proteins that utilise production of proteins
what are some problems with first generation mAbs?
can provoke an immune response
short half-life
also can’t activate human complements
how can the lack of activation of human complements be addressed?
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.
what is an alternative approach to delivering entire genes?
using oligonucleotides
short antisense oligonucleolotides specifically
what is mipomersen used for?
to treat hypercholesterolaemia
what is the comparison in size between conventional drugs and biopharmaceuticals?
biopharmaceuticals are larger in size compared to conventional drugs
what is the comparison in synthesis between conventional drugs and biopharmaceuticals?
conventional drugs are easier to synthesise in identical batches
what is the relationship between dose and effect for conventional drugs and biopharmaceuticals?
conventional drugs have a more predictable relationship between dose and effect whereas biopharmaceuticals are less predictable
what is gene therapy?
a strategy used to deliver a functioning copy of a defective gene to a target cell by using a suitable vector.
give an example of second generation biopharmaceuticals?
insulin synthesised to have a longer duration of action
what is an advantage of biopharmaceuticals over conventional drugs?
biopharmaceuticals have a lower incidence of adverse effects
how does an antisense oligonucleotide bring about its therapeutic effect?
by blocking the translation of mRNA once it has reached the ribosome
give some example of the therapeutic applications of gene therapy:
gendicine: treatment of replacing faulty P53 protein causing head and neck cancer
glybera: Aden-associated virus construct
strimvelis: ex-vivo therapy to reat SCID
