2:00 Gene therapy takes aim at a new target: common disease.
7:00 PCSK-9 variants and the audacious goals of Verve Therapeutics.
13:14 Crispr 2.0
16:20: Lipid nanoparticles: “the molecule of the year and quite probably the decade.”
21:40 LNP packages containing mRNA to produce both the means of editing the PCSK-9 gene and the guide RNA that will deliver them to the correct spot in the genome are taken up by the liver because “that is what the liver likes to do.”
26:51 Amyloidosis, a rare (or maybe not so rare?) condition stems from misfolded proteins produced by the liver that form dangerous fatty clumps in the bloodstream. Fatbergs in the liver!
Ten years ago, the only true treatment for a fatal form of amyloidosis was to transplant both heart and liver. Last month, researchers published preliminary data from a first attempt by Intellia Therapeutics to do editing in vivo in the human liver. The results? “Better than anyone had dared to hope,” says Kiran. Here’s the article for anyone who wants details.
AND FINALLY: What’s next?
41:20 Genes like PCSK-9 and TTR that you can safely turn off to fix the problem will be relatively rare, says Kiran. Other situations are likely to be more complicated – involving trade-offs and multiple genes and genes that need to be corrected, not merely shut down.
45:46 A Covid silver lining: the pandemic has forced us to develop a huge capacity to make LNP-based drugs – “that manufacturing capacity is not going to go away.”
47:00 Optimistic about the next 5-10 years
A cardiologist and Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, Kiran Musunuru is a clinician and a researcher whose important work has moved the ball forward on gene therapy. As co-founder and scientific advisor to Verve Therapeutics, Kiran has a special perspective – an insider’s view of the business, from someone who is both an academic (MD, PhD, MPH) and a humanist at heart. No one better to discuss the news that broke last month, with early good reports on treatment for ATTR amyloidosis that uses lipid nanoparticles to deliver a CRISPR package for in vivo editing. Is this the breakthrough moment we’ve been waiting for since the Human Genome Project began? Yes, says Kiran Musunuru, going all-in on the next 5 years.