Forward-looking Research: The Potential of New Genetic Technologies
Presentation Transcript
- James F. Gusella, PhD Center for Human Genetic Research - Massachusetts General Hospital Forward-looking Research: The Potential of New Genetic Technologies
- Effective ND Therapies This is the ultimate mission of Norrie Disease investigators/clinicians
- Potential types of therapeutic intervention
- Pharmaceutical: traditional small molecule drugs
- Biological: proteins, gene manipulation
- Medical device
- Therapeutic development
- It requires 3 different kinds of research:
- Basic/Discovery research
- Applied/translational research
- Clinical trial research
- Why not just guess at a drug?
- Why not just guess at a target or test all of them?
- How do mutations cause disease symptoms?
- Why? To identify a specific molecular target or pathway against which an effective drug can be developed
- How? Basic Research
- How to define the effects of the Norrie disease mutation?
- Advances in high throughput biology – permits unbiased mining of large datasets and definition of global pathway changes
- Advances in DNA sequencing are opening up the search for factors that modify disease
- Advances in stem cell technology will permit the study of norrin function in authentic human cells of different types
- Genetic models with inbred mice are identical clones of each other 50 72 80 92 111 150
- Manual DNA sequencing: from the era of Norrie gene discovery
- Only a few hundred thousand bases per person per year
- Semi-automated DNA sequencing: Led to sequencing of the entire human genome for ~3 billion dollars
- Automated “next-generation DNA sequencing:
- Currently can provide full genome sequence for $5,000-$20,000
- Expected to drop to less than $1,000 with 1-2 years
- Realistic to sequence whole genomes and for other applications to more rapidly identify factors that modify disease – identify targets and pathways for therapeutic intervention that are already validated in humans or human cells
- Advances in applied research
- Pharmaceutical companies are beginning to investigate a pathway-based therapeutic approach
- Human cell models may be more predictive of potential therapeutic benefit than non-human models
- Research advances in the ability to manipulate gene expression: RNA interference, microRNAs, sequence specific targeting
- Research advances in experimental delivery systems for gene-based biological
- Empowering the Research Pipeline
- Research requires the cooperation and participation of patients at all stages for:
- detailed description of disease in all its aspects
- biological samples for discovery and applied research
- clinical research into effectiveness of candidate interventions
- Thank you