What is the future of Genome Medicine?
The meeting by that same name that I’m at down here in La Jolla is all about tackling this question and the line up of speakers today on the first day is amazing. I’m speaking about IPS cells as a basis for personalized medicine tomorrow morning so that’s exciting.
As time permits I’m going to try to do a bit of stream of consciousness live blogging of the event so here goes. Don’t expect everything to be a full sentence…
Today got started with a cool presentation on diagnosing brain pathogens by deep sequencing, which is a remarkable technology. The first case presented was on a patient with a tap worm in the brain that could only be diagnosed via genomics.
CRISPR innovator Feng Zhang next discussed genome editing.
He started by talking about harvesting research tools from natural diversity. They asked, “Are there other CRISPR effectors that remain to be discovered?” They computationally looked for the answer and found a long list of candidates. They found for instance Cpf1, C2c1-c3. They felt C2c2 was more interesting and is a guided RNase. Upon recognition of the target, the enzyme becomes activated but becomes a non-specific RNase at that point. Naturally targets phage via immunity and PCD. How can C2c2 be useful? Sherlock method for diagnostics of biological pathogens. Using a guide that “looks for” target sequence using a degradation-activated reporter based on targeting pathogen RNAs. Example of Zika. Sensitive to aM level in experiments. I wonder: could the same be done with CRISPR for pathogen DNA? He also briefly mentioned natural system of genome rearrangement in organisms such as one particular ciliate.
Ante “Bill” Lundberg, CSO of CRISPR Therapeutics, spoke next on CRISPR Therapeutics for Sickle Cell and B-thalassemia, both diseases of B-globin. The dramatic increase in characterized disease-causing genes lays the foundation for genomic medicine. A key question, once you edit cells in the body? What will work efficiently for delivery? Not everything can be done on cells outside the body. Goal is to get fetal hemoglobin elevation. They gene edited patient CD34+ HSCs as their therapeutic modulation. He also discussed safety considerations including off-target editing and unintended consequences of on-target editing. The rigorously probe for these including in animals. They get about 90% editing in the lab and strikingly very similar level at clinical scale, which is impressive. IND studies are underway.
He also talked about the National Academies report released this Valentine’s Day on non-heritable and heritable human gene editing. More discussion is needed going forward by all of us, he said. His own personal view is one of caution on germline editing and only rare applications are imagined plus PGD is an existing option. “Treat the patient, not the germline”.
Great session to start the conference.