This article and associated images are based on a poster originally authored by Andrej Alendar, Shoval Tirman, James Murphy, Liv Austenna, Ilaria Falcitori, Iris Grossman, Yaniv Erlich, Paloma Giangrande, Omer Weissbord and Omer Ziv and presented at ELRIG Drug Discovery 2024 in affiliation with Eleven Therapeutics.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
DELiveri®: Why and how?
Cell-specific delivery of RNA therapeutics
- Reduced toxicity: The drug penetrates relevant tissue only
- Favorable CMC profile
- Potential for long durations of effect
- A proven concept (i.e., GalNAc)
- A multi-billion-dollar market for ex-hepatic organs (a)
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
Our technology
- A high-throughput, hypothesis-free screening platform harnessing the combinatorial power of DNA-encoded libraries (b)
- Unmatched sensitivity due to a synthetic biology circuit that converts cells into molecular radars for nucleic acid delivery (c)
- The DELiveri® circuit exponentially boosts the signal-to-noise ratio of conjugates capable of productive delivery to the cytoplasm (c)
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
The power of DELiveri®
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
- DELiveri® boosts the dynamic range of the library by orders of magnitude – enabling the identification of highly potent delivery conjugates (a, b)
- DELiveri® screens demonstrate strong separation between positive and negative controls (c)
Internal consistency of DELiveri® screens
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
- DELiveri screens are highly robust across biological replicates, independent screens, molecular duplicates and stereoisomers
Strong structure-activity relationship
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
- Conjugates with similar structural properties score similarly in DELiveri® screens (a, b)
- Multiple cheminformatics features correlate with the DELiveri® screen score, demonstrating a strong structure-activity relationship (c)
Hit identification and validation
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
- Hits from DELiveri screens (a, b) score highly in independent validation experiments (c)
- Strong correlation between DELiveri screens and follow-up hit validation experiments
DELiveri® screens across cell types
Image Credit: Image courtesy of Andrej Alendar et al. in partnership with ELRIG (UK) Ltd.
- We successfully carried out screens across a diverse array of cell lines and primary cells
Conclusions
- A high-throughput, hypothesis-free screening platform harnessing the combinatorial power of DNA-encoded libraries (b)
- Unmatched sensitivity due to a synthetic biology circuit that converts cells into molecular radars for nucleic acid delivery (c)
- The DELiveri® circuit exponentially boosts the signal-to-noise ratio of conjugates capable of productive delivery to the cytoplasm (c) Hit Identification and Validation
- DELiveri® decodes the nucleic acid delivery properties of tens of thousands of compounds in a single pot reaction across various cell types.
- Our technology accurately predicts the success rates of each compound in further validation assays.
- We identified highly potent hits, which we independently validated and benchmarked against cholesterol, an established non-cell-specific delivery molecule.
- We demonstrated the power of the DELiveri® platform to function across a diverse array of cell types.
- Our DELiveri® platform is poised to enable oligonucleotide therapeutics to be applied beyond the liver.
About Eleven Therapeutics 
We are a cross-disciplinary group of entrepreneur scientists that came together in 2020 to usher in the next generation of RNA technologies. Coming from leading academic institutions, well-established pharma companies, and high-stress military environments, we share the single goal of creating scalable processes to program RNA therapies, focusing initially on treating respiratory diseases.
About ELRIG (UK) Ltd.
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