Gene TherapyGene TherapyDelivering genes into cellsDelivering genes into cells

VectorsVectors In genetics the term vector describes In genetics the term vector describes

something capable of delivering genes into something capable of delivering genes into cells.cells.

So bacterial plasmids are an obvious exampleSo bacterial plasmids are an obvious example Other examples include :Other examples include :Liposomes – large vesicles which fuse with a cell Liposomes – large vesicles which fuse with a cell

surface membranesurface membraneViral DNA (which is specialized at entering Viral DNA (which is specialized at entering

cells), often in the form of bacteriophages, cells), often in the form of bacteriophages, this is a virus which is specialized at injecting this is a virus which is specialized at injecting its DNA into Bacteria – this overcomes the its DNA into Bacteria – this overcomes the problem of heat shocking.problem of heat shocking.

Hybrid vectors with the properties of both Hybrid vectors with the properties of both ‘phages’ and plasmids (cosmids, phagemids ‘phages’ and plasmids (cosmids, phagemids and phasmids)and phasmids)

Somatic gene therapySomatic gene therapy Gene therapy is inserting genes Gene therapy is inserting genes

into a living organism (usually a into a living organism (usually a human) to overcome some human) to overcome some genetic defect genetic defect

It does It does not not influence the whole influence the whole organisms geneticsorganisms genetics

Only the cells which have had Only the cells which have had genes introduced will be affected, genes introduced will be affected, and only until those cells die.and only until those cells die.

The persons local genotype is The persons local genotype is temporarily temporarily alteredaltered

The change will not be passed to The change will not be passed to offspringoffspring

Diagram showing one method of somatic gene therapy, using a genetically modified virus which is then allowed to infect body cells with the useful gene.

Somatic gene therapy – Somatic gene therapy – cystic fibrosiscystic fibrosis

In cystic fibrosis a pair of In cystic fibrosis a pair of recesssive genes (alleles) for recesssive genes (alleles) for a transmembrane protein a transmembrane protein are causing a malfunctioning are causing a malfunctioning of the protein. The result is of the protein. The result is excessively sticky mucus in excessively sticky mucus in the airways which can lead the airways which can lead to suffocationto suffocation

Introducing the functional Introducing the functional gene (augmentation) into the gene (augmentation) into the airways using liposomes in airways using liposomes in sprays has proven successfulsprays has proven successful

Somatic gene therapy – Somatic gene therapy – killing cellskilling cells

In the treatment of In the treatment of cancer, cancer cells have cancer, cancer cells have similarly been sprayed similarly been sprayed with viral vector cells with viral vector cells that contain information that contain information for making antigensfor making antigens

The antigens are then The antigens are then expressed on the surface expressed on the surface of the cancer cells and of the cancer cells and are destroyed by the are destroyed by the body’s own immune body’s own immune systemsystem

Killer T cell destroys a cancer cell marked out with viral antigens

Gene therapy - germ line Gene therapy - germ line therapytherapy

‘‘germ’ means seed (i.e. sperm or egg)germ’ means seed (i.e. sperm or egg) This type of therapy involves This type of therapy involves

introducing a gene/genes to sperm or introducing a gene/genes to sperm or egg, or even a zygoteegg, or even a zygote

This additional functional gene will This additional functional gene will therefore be in all the adult body cellstherefore be in all the adult body cells

Genetic disorders in new individuals Genetic disorders in new individuals could be eliminated by this technique could be eliminated by this technique e.g. sickle cell anaemiae.g. sickle cell anaemia

However, an ethical committee has However, an ethical committee has rendered this type of gene therapy rendered this type of gene therapy illegalillegal

Arguments against germ Arguments against germ line therapyline therapy

It may be possible to accidentally It may be possible to accidentally modify the DNA in such a way that the modify the DNA in such a way that the germ cells could develop a germ cells could develop a newnew disease or interfere with Human disease or interfere with Human EvolutionEvolution

This type of therapy is essentially a This type of therapy is essentially a modification of the human genome modification of the human genome which raises moral issues, especially which raises moral issues, especially as a modified human will pass his/her as a modified human will pass his/her modification to any offspringmodification to any offspring

For some this comes uncomfortably For some this comes uncomfortably close to the idea of creating a master close to the idea of creating a master race for those who can afford it.race for those who can afford it.

XenotransplantationXenotransplantation Xeno (foreign) transplantation Xeno (foreign) transplantation

is the transplanting of animal is the transplanting of animal organs into humans (e.g. pig organs into humans (e.g. pig hearts into humans)hearts into humans)

This has been carried out in This has been carried out in situation where the only other situation where the only other option is deathoption is death

The problem is, owing to the The problem is, owing to the foreign antigens, the organ is foreign antigens, the organ is soon rejected by the hosts soon rejected by the hosts white blood cellswhite blood cells

In 1984 Californian “Baby Fae” made news as the first baby to have a baboon heart transplant owing to a lack of suitable donors.

Gene therapy - Gene therapy - xenotransplantationxenotransplantation

Introducing human nucleotidase enzyme Introducing human nucleotidase enzyme into the germline of pigs alters their organsinto the germline of pigs alters their organs

The change reduces the chance of organ The change reduces the chance of organ rejection in humansrejection in humans

Problems with xenotransplantation include:Problems with xenotransplantation include:- problems with pigs having a normal problems with pigs having a normal

lifespan of 15 years so organs age lifespan of 15 years so organs age prematurelyprematurely

- Pig body temp. is 39 C.Pig body temp. is 39 C.- Muslims oppose use of pork productsMuslims oppose use of pork products- Concerns about animal diseases passing to Concerns about animal diseases passing to

humans (Phumans (PorcineorcineEEndogenousndogenousRRetroetroVVirusirus)) Animal welfare activists object to the genetic development of animals for human organ transplantation

XenotransplantatioXenotransplantation for type I n for type I DiabetesDiabetes

Introducing Islets of Langerhans from Introducing Islets of Langerhans from donors has been effective in curing Type I donors has been effective in curing Type I diabetes.diabetes.

However, as an autoimmune response was the cause However, as an autoimmune response was the cause of damage to the beta cells in the first place, memory of damage to the beta cells in the first place, memory cells pose a significant threat.cells pose a significant threat.

For this reason extra powerful autoimmune drugs For this reason extra powerful autoimmune drugs need to be used (these bring risks).need to be used (these bring risks).

Genetic modification of pigs to prevent the expression Genetic modification of pigs to prevent the expression of antigens on their pancreatic cells would mean of antigens on their pancreatic cells would mean porcine pancreas could be transplanted into a type I porcine pancreas could be transplanted into a type I diabetes patient providing a permanent cure.diabetes patient providing a permanent cure.