Are We Nearing the Plateau of Productivity for in-vivo Therapeutic Gene Editing?

White Paper

August 24, 2021

Are We Nearing the Plateau of Productivity for in-vivo Therapeutic Gene Editing?

Michael Rice, MS, MBA, VP, & Head of Advanced Therapeutics Practice, Cello Health BioConsulting
Beth Fordham-Meier, CLP, VP, Business Development, Head of Corporate & BD Strategy Practice, Cello Health BioConsulting
Andrew Y. Ng, PhD, Senior Consultant, CNS Practice Lead, Cello Health BioConsulting

Amidst success of in vivo adeno-associated virus (AAV) based gene therapies, the gene therapy community awaits key outcomes from next month’s Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) meeting discussing toxicities and deaths associated with high titer AAV dosing and potential long-term adverse events. While this discussion evolves, a significant advance for in vivo non-viral gene editing was published in a landmark report by Intellia and Regeneron demonstrating, for the first time, the safety and efficacy of non-viral, lipid nanoparticle (LNP) administered CRISPR-Cas9 gene editing in the human liver. The report demonstrated that NTLA-2001 was efficiently delivered to the liver and knocked out the TTR gene in hepatocytes with a single dose treatment. Accumulations of misfolded transthyretin in systemic tissues is responsible for Amyloidosis (ATTR), which presents clinically with polyneuropathy and/or cardiomyopathy. While chronically administered drugs (tafamidis/Vyndaqel, inotersen/Tegsedi and patisiran/Onpattro) for ATTR have recently been developed, one-time treatment of NTLA-2001 has the potential for lifelong reduction of TTR protein and reversing disease progression……More by clicking the Download pdf green button above.