BACKSynthetic mRNAs for treatment of EBV-associated diseases
[Licensing negotiation in progress]
[Invitation for Expression of Interest- Deadline: 26 March 2024]
We are inviting expressions of interest (EoI) for commercializing “Synthetic mRNAs for treatment of EBV-associated diseases technology. The innovation is developed by Professor LO Kwok Wai, Professor of Department of Anatomical and Cellular Pathology of The Chinese University of Hong Kong (CUHK Reference: 22/MED/1180).
The Technology
A remarkably wide range of lymphoid malignancies and two distinct types of human epithelial cancer, nasopharyngeal carcinoma (NPC) and EBV-associated gastric cancer (EBVaGC) are driven by the persistent latent infection of Epstein-Barr virus (EBV). Collectively these EBV-associated tumors impose a global disease burden estimated to reach 265,186 new cases per year at 2017. Among these EBV-associated cancers, >40% are nasopharyngeal carcinoma (NPC) that are prevalence in South China and Southeast Asia. The well-documented viral-cell interaction in tumorigenesis indicates that targeting EBV is an efficient approach to eradicate these cancers. Notably, the unique episomal nature of the EBV genome in the tumor cells implies induction of cell death by reactivation of viral lytic cycle is an attractive approach to cure the EBV-associated cancers. When the latent EBV viruses are induced into lytic cycle, the immediate-early (IE) proteins, BZLF1 and BRLF1 must be expressed and further activated the transcription of early and late proteins to progress. Reactivation of the virus from latency is dependent on expression of the viral BZLF1 and BRLF1 proteins. The present disclosure is the application of synthetic mRNAs to efficiently activate EBV lytic genes in EBV-latent infected cells. These synthetic modified mRNAs can be packaged into lipid nanoparticles (LNPs) or other non-viral delivery systems and then delivered to the tumor cells to translate an artificial protein containing linked DNA binding and transcriptional activation domains that specifically activates the transcription of EBV-encoded lytic genes such as BZLF1, BRLF1 and BGLF4. The mRNA nanomedicine technology provided herein overcomes the highly complex regulatory mechanisms of EBV lytic gene expression. By taking advantage of the high copy number of EBV episomes in the EBV-infected cancer cells, the synthesized designed mRNAs enable highly efficient BZLF1 and BRLF1 expression to reactivate EBV lytic cycle. This artificial activation of EBV-lytic gene transcription, including transcription of the EBV-encoded kinase BGLF4, enhances efficient conversion of the antiviral non-toxic prodrug form of ganciclovir to its cytotoxic DNA replication inhibitor form for rapidly killing the cancer and bystander cells. The present disclosure provides methods of inducing EBV early lytic cycle genes with high specificity by synthesized modified mRNAs. These synthetic mRNAs are first-in-class therapeutic drugs slow or stop cancer cell growth in vitro and in vivo, being innovative therapeutic strategies effectively activating viral lytic genes for oncolytic therapy of EBV-associated cancers.
Commercialization
The technology is now available for licensing on an exclusive basis. In order to fully realize the benefit of the technology, we expect substantial investment is necessary to enable further research and development. In addition to the financial commitment, the licensee is expected to have the appropriate expertise as well as plans in marketing and strategizing the end product to ensure successful transfer of the technology to the society. Previous or existing business involvement and experience in this area is a plus.
This invitation of expression of interest is without prejudice. We also stress that this invitation is not a tender, and the University is not bound to accept any offer, or to accept the highest monetary offer, as there are additional considerations (such as the widest possible benefit to the community) that we, as a public institution, will need to take into consideration.
Synthetic mRNAs for treatment of EBV-associated diseases
[Licensing negotiation in progress]
[Invitation for Expression of Interest- Deadline: 26 March 2024]
We are inviting expressions of interest (EoI) for commercializing “Synthetic mRNAs for treatment of EBV-associated diseases technology. The innovation is developed by Professor LO Kwok Wai, Professor of Department of Anatomical and Cellular Pathology of The Chinese University of Hong Kong (CUHK Reference: 22/MED/1180).
The Technology
A remarkably wide range of lymphoid malignancies and two distinct types of human epithelial cancer, nasopharyngeal carcinoma (NPC) and EBV-associated gastric cancer (EBVaGC) are driven by the persistent latent infection of Epstein-Barr virus (EBV). Collectively these EBV-associated tumors impose a global disease burden estimated to reach 265,186 new cases per year at 2017. Among these EBV-associated cancers, >40% are nasopharyngeal carcinoma (NPC) that are prevalence in South China and Southeast Asia. The well-documented viral-cell interaction in tumorigenesis indicates that targeting EBV is an efficient approach to eradicate these cancers. Notably, the unique episomal nature of the EBV genome in the tumor cells implies induction of cell death by reactivation of viral lytic cycle is an attractive approach to cure the EBV-associated cancers. When the latent EBV viruses are induced into lytic cycle, the immediate-early (IE) proteins, BZLF1 and BRLF1 must be expressed and further activated the transcription of early and late proteins to progress. Reactivation of the virus from latency is dependent on expression of the viral BZLF1 and BRLF1 proteins. The present disclosure is the application of synthetic mRNAs to efficiently activate EBV lytic genes in EBV-latent infected cells. These synthetic modified mRNAs can be packaged into lipid nanoparticles (LNPs) or other non-viral delivery systems and then delivered to the tumor cells to translate an artificial protein containing linked DNA binding and transcriptional activation domains that specifically activates the transcription of EBV-encoded lytic genes such as BZLF1, BRLF1 and BGLF4. The mRNA nanomedicine technology provided herein overcomes the highly complex regulatory mechanisms of EBV lytic gene expression. By taking advantage of the high copy number of EBV episomes in the EBV-infected cancer cells, the synthesized designed mRNAs enable highly efficient BZLF1 and BRLF1 expression to reactivate EBV lytic cycle. This artificial activation of EBV-lytic gene transcription, including transcription of the EBV-encoded kinase BGLF4, enhances efficient conversion of the antiviral non-toxic prodrug form of ganciclovir to its cytotoxic DNA replication inhibitor form for rapidly killing the cancer and bystander cells. The present disclosure provides methods of inducing EBV early lytic cycle genes with high specificity by synthesized modified mRNAs. These synthetic mRNAs are first-in-class therapeutic drugs slow or stop cancer cell growth in vitro and in vivo, being innovative therapeutic strategies effectively activating viral lytic genes for oncolytic therapy of EBV-associated cancers.
Commercialization
The technology is now available for licensing on an exclusive basis. In order to fully realize the benefit of the technology, we expect substantial investment is necessary to enable further research and development. In addition to the financial commitment, the licensee is expected to have the appropriate expertise as well as plans in marketing and strategizing the end product to ensure successful transfer of the technology to the society. Previous or existing business involvement and experience in this area is a plus.
This invitation of expression of interest is without prejudice. We also stress that this invitation is not a tender, and the University is not bound to accept any offer, or to accept the highest monetary offer, as there are additional considerations (such as the widest possible benefit to the community) that we, as a public institution, will need to take into consideration.
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Paul Cheung
Office of Research and Knowledge Transfer Services
Professor LO Kwok Wai
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