Objective
- Identify key areas of current or likely future research in monogenic diseases. particularly in the areas of diagnostic, prognostic and treatment advances
Diagnosis of genetic diseases
Currently in the way of screening we have the newborn screening for common disorders (heel prick test) for which there must be a treatment.
We can do more genetic screening for rare presentations
- pedigree
- SNP arrays
- genepanels
- exome sequenceing (cheaper as only sequences expressed genes)
- genome sequencing
Approaching prognosis
Often you have to break difficult news of being diagnosed with a genetic disease
What about treating genetic diseases
These are the levels of therapy available to us at the moment.
- Germ line therapy (issues with this)
- Somatic cell therapy
- Protein replacement therapy
Protein replacement therapy
Limitations
- Multiple infustions
- immune responses to exogenous proteins
- costs lots
- contaminants still possible
- Recombinant lectures now standard
Gene therapy
The essence of this is replacing mutated genes with the wildtype version.
- this replaces the mutated gene, inhibits expression of a damaging protein and kills or protect cells Main methods are nonviral (DNA or RNA) or viral vectors administered in ex vivo (administered into cells outside of body) or in vivo (into the blood stream)
Often these new gene esequences have inducible expression
Gene therapy is the magic bullet for genetic disease
but you need to know 4 things
- Knowledge of the biology of the disease we want to treat You need to know how this will actually be treated
- Natural history as a baseline for efficacy of treatment so you can know if the drug of treatment will work
- An appropriate delivery method a way to get drug or genetic product into the cell
- Means of assessing efficacy A way to see if its working
Delivery vehicles
Engineered or recombinant viral vectors
Modified virus which does not cause disease but can load in DNA
- Adenoviruses (for cancer because this generates immune response)
- Adenoassociated viruses (most commonly used for non cancer uses) (small)
- Retrovirus (lentiviruses) these carry a medium amount of info and integrate into host genome.
example of retrovirus