- RNA Gene Writing™ platform demonstrates continued advances in rewriting to correct pathogenic mutations responsible for phenylketonuria (PKU), alpha-1 antitrypsin deficiency (AATD) and sickle cell disease (SCD) including proof of concept in non-human primates (NHPs) for PKU
- RNA Gene Writing™ technology enables multiplexed full-length gene writing and rewriting with RNA-only delivery to engineer CAR-T cells with robust antitumor activity
- Proprietary lipid nanoparticle (LNP) delivery demonstrates potential to effectively reach cell types beyond hepatocytes including hematopoietic stem cells (HSCs) and T cells
- Dr. Cecilia Cotta-Ramusino, Tessera’s Head of Platform, to highlight these data in an invited symposium presentation today at 8:50 a.m. PDT
SOMERVILLE, MA, USA I May 19, 2023 I Tessera Therapeutics, the biotechnology company pioneering a new approach in genetic medicine known as Gene Writing™, today presented progress across multiple platforms and preclinical programs including increased efficiency in correcting the SCD mutation in preclinical models, increased efficiency in correcting the most common mutation in PKU in mouse and NHP models, and a first-time demonstration of efficient in vivo rewriting in AATD. Additional data were presented on multiplexed full-length gene writing and rewriting to generate tumor-killing CAR-T cells as well as robust delivery efficiency to HSCs and T cells. These new data are being highlighted in an invited symposium talk, three oral presentations and a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place in Los Angeles, California, May 16 – 20, 2023.
“We have made significant strides across our Gene Writing and non-viral delivery platforms,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “In addition to improved efficiency of our RNA Gene Writers in PKU and SCD in preclinical models, we now have preclinical proof of concept data demonstrating their ability to correct the PiZ mutation responsible for alpha-1 antitrypsin deficiency, a serious genetic disease affecting the lungs and the liver with no definitive treatment. Coupled with significant progress in engineering cancer-killing CAR-T cells using our multiplexing approach, we are excited to continue advancing our programs toward our goal of delivering cures to patients suffering from genetic diseases.”
Michael Holmes, Ph.D., Chief Scientific Officer of Tessera added, “Our Gene Writing technology and delivery platforms continue to advance and demonstrate their broad potential to push the boundaries of what is possible in genetic medicine. We are building a strong pipeline of Gene Writers designed to specifically address target indications and our continued progress is a testament to the power of our technology and the highly talented team we have here at Tessera. We look forward to capitalizing on this momentum to translate these novel genetic medicines into the clinic and to make the broadest possible impact for patients.”
Tessera’s Head of Platforms, Cecilia Cotta-Ramusino, Ph.D., will discuss these data in an oral presentation titled “Writing DNA with RNA: Genome Engineering by Target Primed Reverse Transcription” today at 8:50 a.m. PDT.
RNA Gene Writers Efficiently Make True Corrections of Causative Mutations in Multiple Models of Genetic Disease
PKU
- In a humanized mouse model of the R408W mutation (the most common disease-causing mutation for PKU), in vivo rewriting efficiencies of ~40% were observed at doses of 0.5 mg/kg, and in vivo rewriting efficiencies above the 10% expected curative threshold at dosages as low as 0.15 mg/kg
- NHPs showed in vivo rewriting efficiencies at the PAH locus (the gene associated with PKU) of up to 45% in the liver, well above the 10% curative threshold
AATD
- RNA Gene Writers achieved a 28% in vivo correction of the pathogenic PiZ mutation in a humanized mouse model of AATD
- This level of efficiency was associated with an increase in serum concentration of the wild-type alpha-1 antitrypsin (AAT) protein and a significant decrease in aggregates of misfolded mutant AAT protein in mouse livers on histological examination
SCD
- In HSCs derived from patients with SCD, RNA Gene Writers successfully corrected the mutation responsible for the sickling of red blood cells and resulted in 98% expression of wild-type hemoglobin and reduced sickling in vitro
- Additional in vitro and in vivo data showed that edited HSCs retained their normal potential to support hematopoiesis and development of multiple blood cell types
Multiplex Writing to Engineer CAR-T Cells with Robust Antitumor Activity
- RNA Gene Writers can integrate CAR transgenes into T cells at up to 20% efficiency when delivered as all RNA compositions of matter, and lead to functional CAR-T cells that show tumor killing in vitro and in vivo while maintaining high scalability
- RNA Gene Writers can be multiplexed to simultaneously knockout TRAC and B2M with over 80% efficiency in primary T cells and without detectable translocations
- RNA Gene Writers for full-length gene writing and rewriting can be combined to multiplex whole-gene insertion and knockouts simultaneously at high efficiency in primary human T cells
DNA Gene Writer Corrects Severe Ornithine Transcarbamylase (OTC) Deficiency in vivo
- Transient expression of DNA Gene Writer and co-delivery of OTC gene DNA Writer template mediated genomic integration and led to sustained phenotypic correction of orotic acid levels in mice
- DNA Gene Writer enhanced transgene expression over 40-fold in mice and 10-fold in NHPs, raising the possibility that co-delivery of an AAV and Gene Writer can lead to higher, more durable transgene expression at lower vector doses compared to episomal AAV
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 both writing and rewriting of the genome. Rewriting supports the correction of single nucleotides and the deletion or insertion of short DNA sequences. Writing supports replacing exons or introducing entire genes into the genome to restore function or deliver new instructions. 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.
SOURCE: Tessera Therapeutics
Post Views: 54
- RNA Gene Writing™ platform demonstrates continued advances in rewriting to correct pathogenic mutations responsible for phenylketonuria (PKU), alpha-1 antitrypsin deficiency (AATD) and sickle cell disease (SCD) including proof of concept in non-human primates (NHPs) for PKU
- RNA Gene Writing™ technology enables multiplexed full-length gene writing and rewriting with RNA-only delivery to engineer CAR-T cells with robust antitumor activity
- Proprietary lipid nanoparticle (LNP) delivery demonstrates potential to effectively reach cell types beyond hepatocytes including hematopoietic stem cells (HSCs) and T cells
- Dr. Cecilia Cotta-Ramusino, Tessera’s Head of Platform, to highlight these data in an invited symposium presentation today at 8:50 a.m. PDT
SOMERVILLE, MA, USA I May 19, 2023 I Tessera Therapeutics, the biotechnology company pioneering a new approach in genetic medicine known as Gene Writing™, today presented progress across multiple platforms and preclinical programs including increased efficiency in correcting the SCD mutation in preclinical models, increased efficiency in correcting the most common mutation in PKU in mouse and NHP models, and a first-time demonstration of efficient in vivo rewriting in AATD. Additional data were presented on multiplexed full-length gene writing and rewriting to generate tumor-killing CAR-T cells as well as robust delivery efficiency to HSCs and T cells. These new data are being highlighted in an invited symposium talk, three oral presentations and a poster presentation at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place in Los Angeles, California, May 16 – 20, 2023.
“We have made significant strides across our Gene Writing and non-viral delivery platforms,” said Michael Severino, M.D., CEO of Tessera Therapeutics. “In addition to improved efficiency of our RNA Gene Writers in PKU and SCD in preclinical models, we now have preclinical proof of concept data demonstrating their ability to correct the PiZ mutation responsible for alpha-1 antitrypsin deficiency, a serious genetic disease affecting the lungs and the liver with no definitive treatment. Coupled with significant progress in engineering cancer-killing CAR-T cells using our multiplexing approach, we are excited to continue advancing our programs toward our goal of delivering cures to patients suffering from genetic diseases.”
Michael Holmes, Ph.D., Chief Scientific Officer of Tessera added, “Our Gene Writing technology and delivery platforms continue to advance and demonstrate their broad potential to push the boundaries of what is possible in genetic medicine. We are building a strong pipeline of Gene Writers designed to specifically address target indications and our continued progress is a testament to the power of our technology and the highly talented team we have here at Tessera. We look forward to capitalizing on this momentum to translate these novel genetic medicines into the clinic and to make the broadest possible impact for patients.”
Tessera’s Head of Platforms, Cecilia Cotta-Ramusino, Ph.D., will discuss these data in an oral presentation titled “Writing DNA with RNA: Genome Engineering by Target Primed Reverse Transcription” today at 8:50 a.m. PDT.
RNA Gene Writers Efficiently Make True Corrections of Causative Mutations in Multiple Models of Genetic Disease
PKU
- In a humanized mouse model of the R408W mutation (the most common disease-causing mutation for PKU), in vivo rewriting efficiencies of ~40% were observed at doses of 0.5 mg/kg, and in vivo rewriting efficiencies above the 10% expected curative threshold at dosages as low as 0.15 mg/kg
- NHPs showed in vivo rewriting efficiencies at the PAH locus (the gene associated with PKU) of up to 45% in the liver, well above the 10% curative threshold
AATD
- RNA Gene Writers achieved a 28% in vivo correction of the pathogenic PiZ mutation in a humanized mouse model of AATD
- This level of efficiency was associated with an increase in serum concentration of the wild-type alpha-1 antitrypsin (AAT) protein and a significant decrease in aggregates of misfolded mutant AAT protein in mouse livers on histological examination
SCD
- In HSCs derived from patients with SCD, RNA Gene Writers successfully corrected the mutation responsible for the sickling of red blood cells and resulted in 98% expression of wild-type hemoglobin and reduced sickling in vitro
- Additional in vitro and in vivo data showed that edited HSCs retained their normal potential to support hematopoiesis and development of multiple blood cell types
Multiplex Writing to Engineer CAR-T Cells with Robust Antitumor Activity
- RNA Gene Writers can integrate CAR transgenes into T cells at up to 20% efficiency when delivered as all RNA compositions of matter, and lead to functional CAR-T cells that show tumor killing in vitro and in vivo while maintaining high scalability
- RNA Gene Writers can be multiplexed to simultaneously knockout TRAC and B2M with over 80% efficiency in primary T cells and without detectable translocations
- RNA Gene Writers for full-length gene writing and rewriting can be combined to multiplex whole-gene insertion and knockouts simultaneously at high efficiency in primary human T cells
DNA Gene Writer Corrects Severe Ornithine Transcarbamylase (OTC) Deficiency in vivo
- Transient expression of DNA Gene Writer and co-delivery of OTC gene DNA Writer template mediated genomic integration and led to sustained phenotypic correction of orotic acid levels in mice
- DNA Gene Writer enhanced transgene expression over 40-fold in mice and 10-fold in NHPs, raising the possibility that co-delivery of an AAV and Gene Writer can lead to higher, more durable transgene expression at lower vector doses compared to episomal AAV
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 both writing and rewriting of the genome. Rewriting supports the correction of single nucleotides and the deletion or insertion of short DNA sequences. Writing supports replacing exons or introducing entire genes into the genome to restore function or deliver new instructions. 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.
SOURCE: Tessera Therapeutics
Post Views: 54
