Pre-Clinical Research Could Lead to Rapid Development of Dopamine-Producing Neurons; Part of Company’s NIH-Funded Program Seeking Scalable Cell Replacement Therapy Approaches for Parkinson’s Disease
Use of Non-Viral, Self-Amplifying RNA Enhanced and Lengthened Transcription Factor Expression, Driving the Signaling Required for Dopamine-Producing Neuron Development
Findings Presented at 2022 International Society for Stem Cell Research Annual Meeting
SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, presented preclinical regenerative medicine data showing that the company’s proprietary Cell Squeeze® technology can effectively generate dopaminergic (DA) neurons from human-induced pluripotent stem cells (iPSCs) through the single-step delivery of six RNA that encode for specific fate-determining transcription factors. The inclusion of non-viral, self-amplifying RNA in particular was shown to enhance and lengthen transcription factor expression and support DA neuron development. The new findings build upon the company’s recent regenerative medicine research presentations and are aligned with the company’s NIH-funded effort to generate cell replacement therapies for neurodegenerative conditions like Parkinson’s disease. The research was presented at the 2022 International Society for Stem Cell Research (ISSCR) annual meeting.
“Effective cell replacement therapies for diseases including Parkinson’s disease could have significant benefit for patients,” said Jonathan Gilbert, Ph.D., Vice President and Head of Exploratory Research at SQZ Biotechnologies. “Our early preclinical work demonstrates that a single-step delivery of six RNA into iPSCs using the Cell Squeeze® platform can effectively generate dopaminergic neurons. Our continued development of these cell engineering capabilities could potentially enable the creation of future cell replacement therapies.”
While other methods of differentiating iPSCs into specific cell types may often include a lengthy and variable process, the non-viral Cell Squeeze® technology is designed to generate reprogrammed cells through the delivery of fate-determining transcription factors while preserving cell health and limiting adverse effects on baseline gene expression. Cell Squeeze® technology may also allow for control of the timing, intensity, and combination of transcription factor expression to generate high-quality and functional cell products.
Major Findings from Cell Reprogramming Research Presented at ISSCR:
Generation of Dopaminergic Neurons: By combining and delivering Ascl1 saRNA, a key neuronal transcription factor, with five mRNA transcription factors, SQZ scientists were able to differentiate iPSCs into dopaminergic neurons
Significant Increase in Target Gene Expression: A single Cell Squeeze® delivery of saRNA and mRNA transcription factors into human iPSCs induced a 25,000-fold increase in the expression of the FOXA2 gene, a key marker for dopaminergic neurons, in four days
Appearance of Dopaminergic Lineage Markers: After 14 days, the cells expressed dopamine neuronal marker TH and mature neuronal marker MAP2, demonstrating the generation of dopaminergic neurons
- Preservation of Cell Health: Findings verified that 24 hours after processing the iPSCs through a SQZ® chip, there was no significant difference in the expression of 32 common housekeeping genes as well as no meaningful disruption in pluripotent stem cell marker gene and protein expression
Together, these data show the potential of the Cell Squeeze® technology to reprogram cells for regenerative medicine applications, including Parkinson’s disease.
ISSCR Poster Presentation Details
Title: Directed Differentiation of Dopaminergic Neurons from Human Induced Pluripotent Stem Cells through Microfluidic Cell Squeeze® Delivery of Multiple mRNA Encoding Transcription Factors
Poster Board Number: 756
Poster Session: Poster Session 1 Even; Wednesday, June 15, 2022, 7:30 PM – 8:30 PM PST
About SQZ Biotechnologies
SQZ Biotechnologies Company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world. The company has active programs in oncology, autoimmune and infectious diseases, as well as additional exploratory initiatives to support future pipeline growth. SQZ’s proprietary Cell Squeeze® technology can deliver multiple biological materials into many cell types, offering the ability to engineer a broad range of potential therapeutics. With clinical production timelines already under 24 hours, the company has the potential to enable broader patient accessibility through point-of-care manufacturing implementation across multiple therapeutic programs. Our approach could also improve a patient’s treatment journey with no planned hospitalization or preconditioning treatment. The company’s first therapeutic efforts seek to generate target-specific immune responses, both through activation for the treatment of solid tumors and infectious diseases, and by immune tolerance for the treatment of autoimmune diseases. For more information, please visit www.sqzbiotech.com.
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