Description:
C. elegans retrotransposon Cer1 as a delivery mechanism for RNA-based Therapeutics
Princeton Docket # 22-3838
Researchers in Princeton University’s Department of Molecular Biology and the Lewis-Sigler Institute of Integrative Genomics at Princeton University have identified that Cer1 is responsible for carrying a small RNA-mediated signal from germline tissue to neurons, resulting in changed behavior (avoidance of pathogens) in C. elegans. Additionally, Cer1 can be secreted into media, and this media is sufficient to transfer learned information to naïve animals. Unlike viral delivery, Cer1 transposon-mediated delivery of RNA does not require replication or expression of RNA cargo. Additionally Cer1 provides a delivery system to neurons, which are naturally resistant to most other delivery mechanisms.
Cer1 is a Ty3 family retrotransposon in the genomes of some but not all strains of C. elegans. Cer1 forms viral-like particles (capsids).
Applications
- Delivery mechanism for RNA-based therapeutics, including RNA interference molecules
- Crop protection: Behavior modification in plant-parasitic nematodes
- Treatment of pathogenic nematode infections in humans, pets, and livestock.
Advantages
- Allows for delivery to neurons which are resistant to most delivery mechanisms
- Does not require replication or expression of RNA cargo
- Cer1 is a natural product
Intellectual Property & Development Status
Patent protection is pending. Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.
Publications
bioRxiv preprint: https://doi.org/10.1101/2020.12.28.424563, Horizontal and vertical transmission of transgenerational memories via the Cer1 transposon
Rebecca S. Moore, Rachel Kaletsky, Chen Lesnik, Vanessa Cota, Edith Blackman, Lance R. Parsons, Zemer Gitai, Coleen T. Murphy
Cell publication: “The role of the Cer1 transposon in horizontal transfer of transgenerational memory,” Moore, RS, Kaletsky, R, Lesnik C, Cota V, Blackman E, Parsons LR, Gitai Z, and Murphy CT. Cell (2021) Aug 3:S0092-8674(21)00881-3. doi: 10.1016/j.cell.2021.07.022. PMID: 34363756
The Inventors
Coleen T Murphy- Associate Professor and Richard B. Fisher Preceptorship in Integrative Genomics; Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, and Princeton Neuroscience Institute
The Murphy lab studies the process of aging, including the decline of cognitive and reproductive capacities with age, which remain some of the fundamental mysteries in biology. While aging may appear to be an unfortunate consequence of living, recent genetic breakthroughs suggest that aging is a regulated process, rather than the result of cumulative cellular damage. Many chronic and degenerative disorders, including diabetes, cancer, and neurodegenerative diseases, develop in an age-related manner.
The emergence of model systems to study aging and the development of whole-genome approaches is providing an unprecedented glimpse into the processes underlying aging. Our understanding of aging at the molecular level will progress from identifying these global regulators, to defining the genes that they control, to describing the biochemical events that carry out the business of keeping an organism's cells alive. Using C. elegans as a model system, behavioral, genomic, genetic, biochemical, robotic, and computational approaches are undertaken in the Murphy lab to understand the molecular mechanisms of aging.
Rachel T. Kaletsky – is an Associate Research Scholar in the Murphy Lab. Her research involves identifying the tissue-specific transcriptional profiles underlying aging and complex behaviors.
Rebecca S. Moore – was a graduate student in the Murphy Lab (now graduated).
Contact:
Laurie Tzodikov
Princeton University Office of Technology Licensing
(609) 258-7256 • tzodikov@princeton.edu