medical biotechnology summary

medical biotechnology summary

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chapter 1 vaccines vaccines Vaccines were the first-to-be discovered biotechnology ever used. A vaccine triggers an immune response to train the adaptive immune system such that the organism (in this case humans) is better protected against a pathogen/anything else that carries antigens • the vaccine contains antigen(s) that are always carried by the pathogen toward which the vaccine aims to protect → the B cells direct antibodies to epitopes op the antigens

The effectivity of a vaccine depends on the immunogenicity of the epitopes it uses → the more the epitopes mimic the pathogen, the less safe the vaccine becomes: effectivity vs. safety, accept for class VI

The way in which the antigen(s) are carried by the vaccine defines the vaccine strategy, which

distinguishes vaccines into six different classes:

• Class I: killed whole organism → the whole organism is killed either physically or chemically, but it contains still all its (chemically modified) compounds → still effective

− the full pathogen is exposed: lots of different epitopes

− a drawback is that one has to be sure that the organism is fully killed → most dangerous in terms of risk to get ill

• Class II: Life attenuated pathogen → the organism is still alive in the vaccine and the body but has been genetically modified such that its virulence is reduced or removed − virus still replicates so the immune system is constantly producing memory cells + whole organism so lots of epitopes present → most effective − drawbacks: requires a lot of time (modification) and safety checks → to check if the organism doesn’t mutate back to a pathogen again

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• Class III: Vector vaccines → harmless organisms that have been

genetically modified to carry the epitopes of the targeted pathogen (= different organism) → transgenic organism acts as transport vehicle of the epitope and infects the host cells itself homologous recombination to adenoviruses popular nowadays

2 types of vector vaccines:

− replicating (a bit)

− non-replicating: adenoviruses → safer

• Class IV: Subunit vaccines → a complete protein that contains the essential epitope(s) of the pathogen is made by recombinant DNA techniques and is directly injected into the patient − safe

− not very efficient: just one type of protein

• Class V: Peptide vaccines → chemically synthesized small peptides that mimic the essential epitopes of the pathogen are linked to a carrier protein and directly injected − safe − less efficient than Class V: single epitope → may not be sufficiently immunogenic

• Class VI: DNA and RNA vaccines → DNA or RNA is used to let the body produce epitopes of the pathogen itself 3 / 4

the genetic material is not included into the genome because of the risk of disturbing other essential genes → instead it floats in the nucleus apart from the genome RNA is made more stable by pseudo-uridination as this is not degraded by RNAses, therefore increasing the vaccine’s half-life time and thus efficiency linkage of the DNA/RNA to nanoparticles that are favoured for uptake by the cell increase the efficiency even more − drawback: inefficient because of no very pronounce alarming signal as the RNA/DNA is not very distinct from the body’s own genetic material (less than e.g. proteins with their conformations) and the response takes quite some time because the epitopes have to be produced and the vaccine-genetic material has to travel into the cell and its nucleus − in order to be properly expressed, the RNA/DNA needs to have the complete expression/translation module integrated − one of the safest + most efficient vaccine strategies

transfection and transduction in genetic modifications Transfection is the insertion of genetic material in an organism that is not its own. Transduction is the exchange of plasmids between bacteria.

genetic modifications Genetic modifications are carried out by recombinant DNA techniques. Genetic modifications come

in handy for a lot of purposes, especially in medical biotechnology:

− study in vivo functions − generation of disease models − stem cell research and therapy − bioindustry − biomedical industry

Generally, four principle modifications are done:

• Insertion of the genetic material into the DNA transgene

• Episomal addition: genetic material not incorporated into the

DNA (so not really a modification), which is ‘virus’ like → transient modification due to the fact that viral − it may be recognised by immunosurveillance mechanisms that check the DNA − the gene product costs energy to be maintained during replication while it is not advantageous → removal during division • Deletion knock-out

• Replacement: modification of the DNA that is

already present knock-in

Genetic modifications can be either irreversible (very stable) or transient (quite stable) genetic modifications are stable when they are incorporated into the genome (or advantageous to the cell so that is maintained) − viral plasmids have a conditionally modify the DNA (episomally): the plasmid is present when it is advantageous to the cell as its maintenance during replication

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