All cells in a person have the same DNA Yet eye cells differ from nose cells Central dogma of...

All cells in a person have the same DNAYet eye cells differ from nose cells

Central dogma of biologyGenetic engineeri

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Tissue therapy

Other Cells

Matrix MoleculesSelf-Renewal

Soluble Factors

Differentiation

Little, et al. Chemical Reviews (2008).

Low stress levels Regular exercise Enriching experiences Learning new information Healthy diets: rich in antioxidants Avoid excessive drinking

Skin cells iPS cells

Are fully differentiated cells Can not become any other cell type Can only divide to make more

fibroblasts Contact inhibition

Randomly inserts DNA into genome of cells

Can make special retroviruses with whatever gene you want

Can’t really control how many copies of genes

Only turn on a drug resistance gene when stem cell state

Do this by using a gene that is only expressed in stem cells

Add drug resistance to promoter region of that gene

Takes around 16 days for resistance gene to be expressed- some secondary change

Sox2- Self Renewal Oct4- Differentiation switch Klf4- p53 pathway, Oncogene c-Myc- Global Histone Acetylation,

Oncogene

Without Oct 3/4 or Klf: no colonies Without Sox2: rough morphology Without c-Myc: flatter cells, now know

actually can do without c-myc-just very low efficiency

Tried to inject into blastocyst to make baby mice but failed

Final and best test of pluripotency

Still working with mouse model Used different drug selection marker Same 4 genes Much more closely resemble ES cells

Treatment of DNA with bisulfite converts cytosine residues to uracil, but leaves 5-methylcytosine residues unaffected

Introduces specific changes in the DNA sequence that depend on the methylation status of individual cytosine residues

Used Oct3/4, Sox2, Nanog and Lin28

Used the animal’s own cells- no immune rejection!

Transfected with all four genes, but c-myc taken out after time- prevent tumors!

Sickle Cell Anemia has known genetic basis-so target that gene and change it back to normal!

Inject it back into the animal after radiation to reconstitute the whole blood system!

Any disease with a single genetic mutation could be easily cured!

Tissue regeneration after accidents or diseases

“Nanobots” Companies have already started

testing iPS for therapy

No way FDA will approve a therapy with an oncogene

Use of retroviruses can lead to mutations and cancers

So many changes in the DNA can be harmful

Probably hard to target to some areas