Periodic Reporting for period 1 - EPIMODKIT (Generating monoclonal antibodies that selectively and specifically recognize epitranscriptomic modifications.)
Periodo di rendicontazione: 2020-07-01 al 2021-12-31
Epitranscriptomic modifications of RNA can modulate gene expression, contribute to gene regulation, and have emerging roles in several disease contexts. The detection of these modifications relies either on specific chemical methods and mass spectrometry, or on antibodies that can bind a modified base with high selectivity. To tackle these notoriously challenging antigenic targets we have developed a novel vaccination platform based on conjugation of antigens to a highly antigenic microparticle. Here, we succeeded in applying this technology to rapidly elicit excellent antibodies to two RNA modifications (m6A, inosine) and are well on our way to develop antibodies to our third target (pseudouridine). Our results show that m6A and inosine immunization elicited very strong and specific antibody response in mice. Transcriptomic analysis of single cell sorted immune cells allowed us to identify inosine and m6A specific memory B-cell subpopulation and select antibody genes with potentially highest binding levels. We have then produced and tested recombinant human antibodies against inosine and showed that some of these antibodies can recognize and bind inosine protein conjugate and in context of the full RNA. We are currently completing detailed characterizations of affinity and selectivity and are in discussions with several companies both for out-licencing of these as research use materials but also for alternative uses (for example in the context of drug discovery). At the same time, these data provide additional validation of our platform’s ability to elicit and rapidly select antibodies in particularly hard cases where traditional methods have failed. Based on these and other data, we have launched a startup which is currently seeking funding to develop antibodies against tough targets that are highly sought after in the therapeutics market.