Approach is potentially first iPS cell-derived multi-cell-type therapeutic strategy designed to mimic how the human immune system naturally fights disease
Presentations to include additional advances in nucleic-acid delivery and targeted gene insertion
CAMBRIDGE, Mass., May 17, 2023 (GLOBE NEWSWIRE) — Eterna Therapeutics Inc. (Nasdaq: ERNA) (“Eterna”), a life science company committed to realizing the potential of mRNA cell engineering to provide patients with transformational new medicines, and its discovery partner Factor Bioscience (“Factor”) today announced new data on an iPS cell-derived multi-cell-type therapeutic strategy for solid-tumor targeting, as well as advances in nucleic-acid delivery and targeted gene insertion, in eight poster presentations at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting, taking place May 16-20, 2023 at the Los Angeles Convention Center.
“We are pleased to highlight what we believe is the first iPS cell-derived multi-cell-type therapeutic strategy designed to mimic how the human immune system naturally fights disease,” said Matt Angel, Ph.D., Chief Executive Officer and President of Eterna. “This approach has the potential to form the foundation of an entirely new class of cell therapies that could play an important role in treating cancer. We believe that the data we are presenting this week, combined with our recent acquisition of Exacis Biotherapeutics’ immuno-oncology platform, position Eterna to play a leading role in the development of next-generation cell therapies to treat cancer.”
The study (poster #616) demonstrated a scalable platform for generating cell therapies comprising multiple immune cell types, such as NK cells and macrophages, derived from induced pluripotent stem (iPS) cells reprogrammed with mRNA. In vitro studies with lymphoid and myeloid cells showed synergistic killing of SKOV3 ovarian tumor cells. Furthermore, in an effort to improve how the iPSC-derived myeloid cells could target and engage solid tumors, the cells were transfected with mRNA encoding a humanized ROR1-CAR protein. Notably, the ROR1-targeted myeloid cells demonstrated engagement of ROR1 and cytotoxicity toward SKOV3 ovarian cancer cells.
Christopher Rohde, Ph.D., Co-Founder and Chief Technology Officer of Factor and member of the Eterna Scientific Advisory Board, commented, “Our research teams are focused on developing new approaches to overcome the limitations of existing cell therapies. The data presented at ASGCT, including potentially the first iPS cell-derived multi-cell-type therapeutic strategy to treat cancer, highlights the capabilities of our patented technology, in-licensed by Eterna, and the potential of this approach to inform the development of therapies using mRNA cell engineering.”
Eterna and Factor are presenting additional research highlighting advances in nucleic-acid delivery and targeted gene insertion:
Rational Design of Multivalent Ionizable Lipid Delivery Systems for mRNA Delivery to Blood Cells (#563)
The study aimed to identify a lipid formulation capable of efficiently transfecting blood cells, believed to be an ideal target cell for in vivo mRNA cell engineering. The data presented demonstrates efficient delivery of mRNA to target blood cells. This platform has the potential to support numerous ex vivo and in vivo applications of mRNA delivery, including cell reprogramming, gene editing, and protein replacement.
Chemically Modified Single-Stranded DNA Donors Enable Efficient mRNA Gene Editing-Mediated Knock-In in Human iPS Cells (#1065)
This presentation describes a method for high-yield synthesis of single-stranded DNA potentially suitable for targeted insertion applications, including generation of knock-in cell lines. This platform may have applications in the development of both ex vivo and in vivo gene-editing therapies.
Efficient Transgene Knock-In in Human iPS Cells Combined With Small Molecule-Mediated “On-Switch” Yields Clonal Populations of Engineered Tissue-Specific Cells (#1103)
The study aimed to identify methods of differentiating engineered iPS cells to tissue-specific cell populations that uniformly and stably express a desired protein from a transgene inserted by mRNA gene editing. The results presented show temporal control of transgene expression using small molecules during directed differentiation of iPS cells. This methodology has the potential to support the development of engineered cell therapies designed to express therapeutic proteins.
Novel Ionizable Lipids Derived from 2-Hydroxypropylamine and Spermine for mRNA-LNP Delivery (#1262)
The study aimed to identify novel ionizable lipids capable of formulation in lipid nanoparticles (LNPs) exhibiting lower mean particle sizes, higher loading efficiencies, and enhanced protein expression relative to LNPs incorporating the established lipids ALC0315 or DLin-MC3-DMA. A library of ionizable lipids containing elements related to spermine or 2-hydroxypropylamine was developed and evaluated. The data presented show that the lipids identified may serve as components of next-generation, LNP-based mRNA and gene therapies.
Directed Differentiation of Gene Edited iPSCs by Small-Molecule Inhibition of a Transgene-Encoded Protein (#1314)
The study aimed to develop a method for generating transgene-expressing tissue-specific cells derived from engineered iPS cells through the use of small-molecule inhibition of the transgene-encoded protein during differentiation. The results presented suggest that small-molecule inhibition of transgene-encoding proteins may form a key element of directed differentiation process development for knock-in iPS cell lines and may be useful for scaled-up manufacturing of engineered cells.
Gene Editing Proteins with Nickase Functionality Enable Scarless Targeted Gene Insertion in Primary Human Cells (#1516)
The study explored the use of UltraSlice™ gene editing proteins containing cleavage domain variants with nickase functionality for targeted insertion of donor sequences into defined genomic loci. Nickases have the ability to create targeted single-strand breaks, which can favor high-fidelity DNA repair pathways, compared to double-strand breaks, which can be more prone to error and have been associated with cytotoxicity and off-target effects. The data presented demonstrate that the UltraSlice™ nickases enable scarless insertion of donor sequences into defined genomic loci. This methodology may have the potential to improve the safety of in vivo gene insertion by reducing off-target effects of gene-editing nucleases.
mRNA Cell Engineering Enables Rapid Prototyping of Macrophage Gene-Editing Strategies for Cancer Immunotherapy Applications (#1563)
The study assessed an mRNA-based platform to rapidly evaluate macrophage engineering approaches for solid tumor applications. A sequence encoding a CAR targeting ROR1 was inserted into the AAVS1 safe harbor locus in iPS cells, which were then differentiated into macrophages. This technology has the potential to enable the rapid assessment and validation of novel macrophage gene-editing strategies.
About Eterna Therapeutics
Eterna Therapeutics is a life science company committed to realizing the potential of mRNA cell engineering and thereby providing patients with transformational new medicines. Eterna has in-licensed a portfolio of over 120 patents covering key mRNA cell engineering technologies, including technologies for mRNA cell reprogramming, mRNA gene editing, the NoveSlice™ and UltraSlice™ gene-editing proteins, and the ToRNAdo™ mRNA delivery system from Factor Bioscience. NoveSlice™, UltraSlice™, and ToRNAdo™ are trademarks of Factor Bioscience. For more information, please visit www.eternatx.com.
About Factor Bioscience
Founded in 2011, Factor Bioscience develops technologies for engineering cells to advance the study and treatment of disease. Factor’s gene-editing technologies enable the precise deletion, insertion, and repair of DNA sequences in living cells to correct disease-causing mutations, make cells resistant to infection and degenerative disease, modulate the expression of immunoregulatory proteins to enable the generation of durable allogeneic cell therapies, and engineer immune cells to more effectively fight cancer. Factor’s cell-reprogramming technologies enable the generation of clonal lines of pluripotent stem cells that can be expanded and differentiated into any desired cell type for the development of regenerative cell therapies. For more information, visit www.factorbio.com.
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