- A single intravenous administration of Gene Writer™ resulted in an estimated 79% hepatocyte genomic editing with an average of 84% of mRNA transcripts containing the edited sequence in non-human primates (NHPs) at the SERPINA1 locus responsible for alpha-1 antitrypsin deficiency (AATD)
- In vivo proof-of-concept achieved for rewriting at carrier level efficiency (52%) of hemoglobin beta (HBB) gene, the locus responsible for sickle cell disease (SCD), in humanized mice with a single dose of Gene Writer delivered in Tessera's proprietary lipid nanoparticle (LNP)
- Michael Holmes, Ph.D., Tessera's Chief Scientific Officer, will present these data today in the session titled In Vivo Gene Editing in Preclinical Models from 3:30 pm - 4:30 pm CEST
"The continued development of our Gene Writing and delivery platforms have resulted in rewriting efficiencies in preclinical models exceeding what we anticipate will be curative levels for AATD and SCD,” said Michael Severino, M.D., CEO of Tessera Therapeutics. "We believe these data represent an important step towards advancing potentially transformative in vivo genetic medicines for the treatment of two of the largest monogenic diseases, alpha-1 antitrypsin deficiency and sickle cell disease.”
In Vivo AATD Data
Tessera presented new preclinical data from NHP studies in its AATD program using a single dose of RNA Gene Writer formulated with a proprietary LNP delivery vehicle. AATD is a monogenic disease of the liver, resulting in an abnormal form of the alpha-1 antitrypsin (AAT) protein that causes both lung and liver manifestations. Analysis of genomic DNA from whole liver samples collected from treated NHPs showed an estimated 79% rewriting efficiency of the SERPINA1 locus in hepatocytes1 on average. A supporting cDNA analysis demonstrated that an average of 84% of mRNA transcripts contained the edited sequence. These data improve upon the first-time demonstration of NHP proof-of-concept presented recently at the Federation of American Societies for Experimental Biology Meeting on Genome Engineering. Data were also presented of an optimized RNA Gene Writer that achieved therapeutically relevant levels of correction at very low doses in the PiZ mouse model, including an estimated 70% genomic DNA correction in hepatocytes, an average of 70% mRNA correction, and an average of 92% of serum AAT corrected at a dose of 0.05 mg/kg, and an estimated 95% genomic DNA correction in hepatocytes, an average of 93% mRNA correction, and an average of 100% serum AAT corrected at a dose of 0.5 mg/kg.
In Vivo SCD Data
Updated in vivo rewriting results of the HBB locus responsible for SCD in humanized mice showed that Gene Writers formulated in a proprietary LNP developed for delivery to hematopoietic stem cells (HSCs) achieved an average rewriting efficiency of 52% in long-term hematopoietic stem cells (LT-HSCs) after a single intravenous administration. These data build upon the HBB in vivo rewriting data first presented at the American Society of Gene and Cell Therapy 27th Annual Meeting. Additional data show rewriting efficiencies in NHPs exceeding 70% using a surrogate reagent, as well as the maintenance of in vivo HBB edited HSCs and engraftment levels upon secondary bone marrow transplant in humanized mice.
1 Based on the assumption that 60% of liver cells are comprised of hepatocytes
About Tessera Therapeutics
Tessera Therapeutics is pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, with the aim to unlock broad new therapeutic frontiers. Our Gene Writing platform is designed to write therapeutic messages into the genome by efficiently changing single or multiple DNA base pairs, precisely correcting insertions or deletions, or adding exon-length sequences and whole genes. Our proprietary lipid nanoparticle delivery platform is designed to enable the in vivo delivery of RNA to targeted cell types. We believe our Gene Writing and delivery platforms will enable transformative genetic medicines to not only cure diseases that arise from errors in a single gene, but also modify inherited risk factors for common diseases and create engineered cells to treat cancer and potentially autoimmune and other diseases. Tessera Therapeutics was founded in 2018 by Flagship Pioneering, a life sciences innovation enterprise that conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability.
For more information about Tessera, please visit www.tesseratherapeutics.com.
Contact
Kristin Politi, Ph.D.
LifeSci Communications, LLC
