|  Press Release

Tessera Therapeutics Presents New Preclinical Data Highlighting Advancements Across Its Portfolio Programs and Platforms at the American Society of Gene and Cell Therapy 27th Annual Meeting

By Tessera Therapeutics

  • Gene Writing™ platform demonstrates highly efficient in vivo correction of mutation responsible for alpha-1 antitrypsin deficiency (AATD) to wild-type
  • Combination of proprietary lipid nanoparticle (LNP) delivery to long-term hematopoietic stem cells (LT-HSCs) with Gene Writers™ enables in vivo rewriting of the hemoglobin beta (HBB) locus responsible for sickle cell disease (SCD)
  • Gene Writers, combined with proprietary LNP delivery to T cells, allow same-day manufacturing with RNA-only composition to engineer CAR-T cells that cleared tumor in vivo in mice

SOMERVILLE, Mass., May 10, 2024 /GLOBE NEWSWIRE/ Tessera Therapeutics, a biotechnology company pioneering a new approach to genome engineering through the development of its Gene Writing and delivery platforms, today presented progress across its platforms and preclinical programs, including approximately 50% correction of the most common mutation in AATD in vivo in mouse disease models and first-time demonstration of efficient in vivo rewriting of the HBB locus responsible for SCD in humanized mice. Additional data were presented on in vivo correction of pathogenic mutations responsible for phenylketonuria (PKU) and Wilson’s Disease (WD), delivery advances to HSCs and T cells, and whole gene writing to generate tumor-killing CAR-T cells, including proof-of-principle of same-day manufacturing. These new data are shared in four oral presentations and two poster presentations at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place in Baltimore, Maryland, May 7 – 11, 2024.

“We have achieved substantial advances across our Gene Writing and delivery platforms and are focused on driving our therapeutic programs into the clinic,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “We are particularly excited about the highly efficient correction to wild-type that we are seeing in preclinical models for AATD, which exceeds levels seen in asymptomatic carriers of the causative mutation, and the progress we are making on in vivo HSC rewriting in SCD that we believe can enable true correction to wild-type without complex stem cell mobilization and ex vivo cell processing or toxic chemotherapy conditioning.”

Michael Holmes, Ph.D., CSO of Tessera Therapeutics added, “We have demonstrated what we believe are industry leading correction levels and the highest fidelity we are aware of across each of our liver rewriting programs in PKU, AATD, and WD, which is a testament to the exceptional team at Tessera and the power and capabilities of our Gene Writing and delivery platforms.”


  • AATD is a condition in which the liver makes an abnormal form of the alpha-1 antitrypsin (AAT) protein that causes both lung and liver disease
  • In a humanized SERPINA1 mouse model of AATD, Gene Writers achieved an average of 49% rewriting efficiency in whole liver samples at a dose of 0.1 mg/kg, with a fidelity ratio of intended to unintended edits at the target locus of 198 to 1
  • In a transgenic PiZ mouse model in AATD, an average of 55% in vivo correction was observed at a dose of 0.5 mg/kg in whole liver samples, which resulted in an average of approximately 93% of mRNA transcripts being corrected
  • This level of efficiency was associated with a greater than 5-fold increase in serum concentration of the wild-type AAT protein, and a decrease in aggregates of misfolded mutant AAT protein in mouse livers on histological examination


  • Gene Writers achieved therapeutically relevant levels of HBB rewriting in vivo in humanized mice, with an average efficiency of 25-27% in LT-HSCs after a single dose
  • In a repeat dose study, average HBB rewriting levels of 44% were observed upon administering a second dose, suggesting the potential to re-dose and see further increases in correction
  • Additional data showed that HSCs edited in vitro retained their normal function to support hematopoiesis and development of multiple blood cell types upon a secondary bone marrow transplant in mice


  • In a compound heterozygous mouse model containing one allele of the PAH R408W mutation, the most common disease-causing mutation for severe PKU, Gene Writers achieved an average of ~42% rewriting in whole liver samples, which corresponds to an estimated 70% correction in hepatocytes1
  • These rewriting efficiencies were comparable to that achieved in a homozygous mouse model for the R408W mutation and resulted in normalized levels of phenylalanine
  • These results support the potential therapeutic application of Gene Writers for PKU patients that carry at least one copy of the R408W mutation


  • Gene Writers achieved an average of ~60% of alleles corrected in vivo in whole liver samples, which resulted in an average of ~89% of corrected mRNA transcripts in a humanized Wilson’s Disease mouse model with the H1069Q mutation, the most common mutation in North America and Europe
  • This level of efficiency was associated with restored copper physiology, with urine copper excretion diverted to feces and significant reductions in hepatic copper accumulation observed
  • Correction levels of the H1069Q mutation in this mouse model appeared stable for the duration of the study (12 weeks), with corresponding reductions of hepatic copper observed

Engineered CAR-T Cells

  • Gene Writers can integrate CAR transgenes into T cells at an average efficiency of 42% in vitro resulting in the generation of functional CAR-T cells that show tumor killing in vitro and in vivo
  • Proof-of-principle studies in developing a same-day manufacturing process showed the CAR-T cells generated could clear tumor in vivo when administered to mice
  • Additional details will be presented by Kassi Stein, Ph.D., on Saturday, May 11th, 2024, from 11:45 a.m. – 12:00 p.m. EDT


  • Novel LNPs were developed and shown to efficiently deliver a reporter gene to extra-hepatic tissues in vivo, including to an average of ~95% of LT-HSCs in mice and non-human primates (NHPs), and an average of ~80% and ~40% of T cells in mice and NHPs, respectively
  • Gene Writers delivered as LNP-RNA drove an average editing efficiency of 76% in LT-HSCs in vivo in mice treated with a surrogate reagent targeting the beta-2 microglobulin locus

1Based 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 and 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.


Kristin Politi, PhD
LifeSci Communications, LLC