Gene therapy involves delivering genes into cells using vectors like viruses to treat genetic defects. Somatic gene therapy temporarily alters the genes in specific cells of the body but not reproductive cells, so the changes are not inherited. Germline gene therapy modifies sperm, eggs or embryos so changes are inherited, but this raises ethical issues. Xenotransplantation transplants animal organs like pig hearts into humans but organs are rejected, so gene therapy modifies pigs' organs to reduce rejection.

1. Gene TherapyGene Therapy
Delivering genes into cellsDelivering genes into cells

2. VectorsVectors
 In genetics the term vectorIn genetics the term vector
describes something capable ofdescribes something capable of
delivering genes into cells.delivering genes into cells.
 So bacterial plasmids are an obviousSo bacterial plasmids are an obvious
exampleexample
 Other examples include :Other examples include :
Liposomes – large vesicles which fuseLiposomes – large vesicles which fuse
with a cell surface membranewith a cell surface membrane
Viral DNA (which is specialized atViral DNA (which is specialized at
entering cells), often in the form ofentering cells), often in the form of
bacteriophages, this is a virus whichbacteriophages, this is a virus which
is specialized at injecting its DNAis specialized at injecting its DNA
into Bacteria – this overcomes theinto Bacteria – this overcomes the
problem of heat shocking.problem of heat shocking.
Hybrid vectors with the properties ofHybrid vectors with the properties of
both ‘phages’ and plasmids (cosmids,both ‘phages’ and plasmids (cosmids,
phagemids and phasmids)phagemids and phasmids)

3. Somatic gene therapySomatic gene therapy
 Gene therapy is insertingGene therapy is inserting
genes into a living organismgenes into a living organism
(usually a human) to overcome(usually a human) to overcome
some genetic defectsome genetic defect
 It doesIt does notnot influence theinfluence the
whole organisms geneticswhole organisms genetics
 Only the cells which have hadOnly the cells which have had
genes introduced will begenes introduced will be
affected, and only until thoseaffected, and only until those
cells die.cells die.
 The persons local genotype isThe persons local genotype is
temporarilytemporarily alteredaltered
 The change will not be passedThe change will not be passed
to offspring
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.

4. Somatic gene therapy – cysticSomatic gene therapy – cystic
fibrosisfibrosis
 In cystic fibrosis a pair ofIn cystic fibrosis a pair of
recesssive genes (alleles) for arecesssive genes (alleles) for a
transmembrane protein aretransmembrane protein are
causing a malfunctioning ofcausing a malfunctioning of
the protein. The result isthe protein. The result is
excessively sticky mucus in theexcessively sticky mucus in the
airways which can lead toairways which can lead to
suffocationsuffocation
 Introducing the functionalIntroducing the functional
gene (augmentation) into thegene (augmentation) into the
airways using liposomes inairways using liposomes in
sprays has proven successfulsprays has proven successful

5. Somatic gene therapy – killing cellsSomatic gene therapy – killing cells
 In the treatment of cancer,In the treatment of cancer,
cancer cells have similarlycancer cells have similarly
been sprayed with viralbeen sprayed with viral
vector cells that containvector cells that contain
information for makinginformation for making
antigensantigens
 The antigens are thenThe antigens are then
expressed on the surface ofexpressed on the surface of
the cancer cells and arethe cancer cells and are
destroyed by the body’sdestroyed by the body’s
own immune systemown immune system
Killer T cell destroys a cancer
cell marked out with viral
antigens

6. Gene therapy - germ line therapyGene therapy - germ line therapy
 ‘‘germ’ means seed (i.e. sperm or egg)germ’ means seed (i.e. sperm or egg)
 This type of therapy involvesThis type of therapy involves
introducing a gene/genes to spermintroducing a gene/genes to sperm
or egg, or even a zygoteor egg, or even a zygote
 This additional functional gene willThis additional functional gene will
therefore be in all the adult bodytherefore be in all the adult body
cellscells
 Genetic disorders in new individualsGenetic disorders in new individuals
could be eliminated by this techniquecould be eliminated by this technique
e.g. sickle cell anaemiae.g. sickle cell anaemia
 However, an ethical committee hasHowever, an ethical committee has
rendered this type of gene therapyrendered this type of gene therapy
illegalillegal

7. Arguments against germ line therapyArguments against germ line therapy
 It may be possible to accidentallyIt may be possible to accidentally
modify the DNA in such a way thatmodify the DNA in such a way that
the germ cells could develop athe germ cells could develop a newnew
disease or interfere with Humandisease or interfere with Human
EvolutionEvolution
 This type of therapy is essentially aThis type of therapy is essentially a
modification of the human genomemodification of the human genome
which raises moral issues, especially aswhich raises moral issues, especially as
a modified human will pass his/hera modified human will pass his/her
modification to any offspringmodification to any offspring
 For some this comes uncomfortablyFor some this comes uncomfortably
close to the idea of creating a masterclose to the idea of creating a master
race for those who can afford it.race for those who can afford it.

8. XenotransplantationXenotransplantation
 Xeno (foreign) transplantationXeno (foreign) transplantation
is the transplanting of animalis the transplanting of animal
organs into humans (e.g. pigorgans into humans (e.g. pig
hearts into humans)hearts into humans)
 This has been carried out inThis has been carried out in
situation where the only othersituation where the only other
option is deathoption is death
 The problem is, owing to theThe problem is, owing to the
foreign antigens, the organ isforeign antigens, the organ is
soon rejected by the hostssoon 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.

9. Gene therapy -Gene therapy -
xenotransplantationxenotransplantation
 Introducing human nucleotidase enzymeIntroducing human nucleotidase enzyme
into the germline of pigs alters their organsinto the germline of pigs alters their organs
 The change reduces the chance of organThe change reduces the chance of organ
rejection in humansrejection in humans
 Problems with xenotransplantation include:Problems with xenotransplantation include:
- problems with pigs having a normalproblems with pigs having a normal
lifespan of 15 years so organs agelifespan 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 toConcerns about animal diseases passing to
humans (Phumans (PorcineorcineEEndogenousndogenousRRetroetroVVirusirus))
Animal welfare activists
object to the genetic
development of animals
for human organ
transplantation

10. Xenotransplantation forXenotransplantation for
type I Diabetestype I Diabetes
 Introducing Islets of Langerhans fromIntroducing Islets of Langerhans from
donors has been effective in curing Type Idonors has been effective in curing Type I
diabetes.diabetes.
 However, as an autoimmune response was the causeHowever, as an autoimmune response was the cause
of damage to the beta cells in the first place, memoryof 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 drugsFor 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 theGenetic modification of pigs to prevent the
expression of antigens on their pancreatic cells wouldexpression of antigens on their pancreatic cells would
mean porcine pancreas could be transplanted into amean porcine pancreas could be transplanted into a