- RNA Gene Writing™ platform demonstrates clinically relevant levels of in vivo rewriting in the genome of liver cells of non-human primates following a single administration
- RNA Gene Writing™ platform generates tumor-clearing CAR T cells by all-RNA delivery
- RNA Gene Writers™ demonstrate programmable writing to facilitate targeted DNA integration and ability to make small and large changes at the same time in human cells
- DNA Gene Writing™ platform promotes sustained and high levels of transgene expression in non-human primates, potentially extending the reach of conventional AAV-based gene therapy
- Proprietary LNP platform demonstrates the ability to deliver to hematopoietic stem cells and T cells in vivo in both mice and non-human primates
- Company to present at the J.P. Morgan 41st Annual Healthcare Conference on January 9th, 2023, at 1:30 p.m. PST
SOMERVILLE, Mass., Jan. 09, 2023 (GLOBE NEWSWIRE) — Tessera Therapeutics, the biotechnology company pioneering a new approach in genetic medicine known as Gene Writing™, today announced advancements across its Gene Writing™ and non-viral delivery platforms including data demonstrating the potential of Gene Writers™ to write therapeutic messages in the genome of non-human primates (NHPs), to generate tumor-clearing chimeric antigen receptor (CAR)-T cells by all-RNA delivery, and the ability to target non-viral delivery systems to hematopoietic stem cells (HSCs) and T cells. The Company will highlight these data and other recent progress in a presentation at 1:30 p.m. PST today at the 41st Annual J.P. Morgan Healthcare Conference taking place in San Francisco, California.
“These important new data sets in non-human primates represent a pivotal milestone for our Company and speak to the immense potential of Gene Writing to make almost any type of genetic change necessary to address human disease,” said Michael Severino, M.D., Chief Executive Officer of Tessera and CEO-partner of Flagship Pioneering. “Our preclinical studies demonstrate that we can deliver our Gene Writers to the right location, in the liver and beyond, and make therapeutic alterations to the genome. In genetic medicine, success in NHPs is highly predictive of success in human trials, and with these data, we are one step closer to bringing our novel genetic medicines into the clinic.”
Michael Holmes, Ph.D., Chief Scientific Officer of Tessera, added, “While the fields of genome engineering and non-viral delivery have made important strides, they have not yet yielded the tools needed to safely deliver and broadly engineer the genome to drive potentially curative changes in target cells with high efficiency, specificity, and fidelity. Building on nature’s way of writing DNA, we can engineer our Gene Writers to broadly write and rewrite DNA sequences in the genome across a wide range of cell types in vivo, including liver, hematopoietic stem cells, and T cells with all-RNA compositions that permit the use of non-viral delivery platforms. This represents a true feat for the genetic medicine field.”
Tessera is developing a broad set of Gene Writer™ systems to make nearly any type of genetic change needed to treat or cure disease. RNA Gene Writers™ are based on retrotransposon biochemistry and use target primed reverse transcription to engineer the genome in diverse ways, without making double-strand DNA breaks, using all-RNA compositions of matter. The Company’s proprietary non-viral lipid nanoparticles (LNPs) are designed to deliver Gene Writers™ to targeted tissues, potentially enabling the application of Gene Writing™ therapies in vivo. DNA Gene Writers™ are based on recombinase or transposase element biochemistry and have been engineered to integrate a therapeutically relevant payload of choice.
RNA Gene Writers™ Make Precise Alterations, Insert Exon- and Gene-Length Sequences Using All-RNA Compositions
Tessera’s RNA Gene Writers™ demonstrate the ability to make a precise, single base pair alteration in vivo at the causative locus for phenylketonuria (PKU) in NHPs using all RNA-LNP compositions of matter, achieving clinically relevant rewriting efficiencies, with up to 35% of alleles in the liver edited seven days after a single intravenous administration. Additionally, data from studies in other preclinical models demonstrate that RNA Gene Writers™ can correct to wild type the mutation that causes sickle cell disease at a high efficiency, resulting in the nearly complete conversion of protein production from mutated sickle-causing hemoglobin to normal hemoglobin.
Additional data demonstrate the ability to write longer sequences and entire genes with high efficiency and specificity. RNA Gene Writers™ were engineered to insert DNA sequences at defined target sites in the genome, including the insertion of a 150-base pair sequence with single-nucleotide precision at efficiencies of up to 40% of alleles in human cell lines. This suggests the potential for RNA Gene Writers™ to insert entire exons or ultimately genes at their native site to correct genetic loci where multiple mutations may occur in a patient population. RNA Gene Writers™ have shown integration of functional CAR templates into primary human T cells with all-RNA delivery and demonstrated potent tumor-killing activity in vitro and in vivo in mouse tumor models. Furthermore, multiplexing – combined writing and rewriting to make small and large changes simultaneously – can be achieved and may better enable next-generation cell-based therapies.
DNA Gene Writers™ Drive Durable Transgene Expression
Tessera’s DNA Gene Writers™, when co-administered with an adeno-associated virus (AAV) containing the DNA template, promoted durable expression of a transgene in the liver of NHPs, resulting in sustained expression at levels 5x higher than achieved with an episomal AAV control, even after partial hepatectomy and despite being delivered at one-fifth the dosage.
Novel LNP Delivery Highlights Potential for In Vivo Gene Writing in Extrahepatic Tissues
In NHP studies, Tessera’s proprietary LNPs demonstrated the ability to deliver to HSCs and T cells in vivo with >30%, and >45% efficiency, respectively, demonstrating the potential for the creation of additional in vivo Gene Writing™ therapies.
The Company plans to present these data at future scientific conferences.
About Tessera’s Gene Writing™ Technology
Gene Writing™ can make permanent therapeutic alterations to the human genome, offering the potential for a new category of genetic medicines with broad therapeutic applications both in vivo and ex vivo. Tessera’s Gene Writer™ systems, which can be delivered as RNA or DNA, enable the correction of single nucleotides, the deletion or insertion of short DNA sequences, and the writing of exons or entire genes into the genome. Gene Writers™ are based on nature’s genome architects, mobile genetic elements (MGEs)—the most abundant class of genes across the tree of life, representing approximately half of the human genome. Tessera’s research engine further engineers the discovered Gene Writer candidates to optimize for efficiency, specificity, and fidelity—enabling the full spectrum of genome editing outcomes and bringing the possibility of curing serious diseases with a genetic basis closer to reality.
About Tessera Therapeutics
Tessera Therapeutics is pioneering Gene Writing™, which consists of multiple technology platforms designed to offer scientists and clinicians the ability to write therapeutic messages into the human genome, thereby potentially curing diseases at their source. Coupled with pioneering innovations in non-viral delivery to introduce therapeutic messages where they are needed, Gene Writing™ enables the correction of single nucleotides, the deletion or insertion of short DNA sequences, and the writing of entire genes into the genome, offering the potential for a new category of therapeutics to realize the promise of genetic medicine. 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.
Anne Shelton, M.D., Ph.D.
LifeSci Communications, LLC