RNA editing and post-transcriptional modification is emerging as a key epigenetic mechanism for fine tuning genetic diversity and RNA function of particular importance in the brain. However, while some RNA editing processes have been relatively well described, other RNA modifications are poorly understood and many questions remain about the true significance of these processes to neurological function in health and disease. Recent developments in deep sequencing approaches have highlighted the number and extent of RNA base modifications, but tools with the requisite high specificity are required to understand the role these changes play in neurophysiology at the developmental, regional, cellular and subcellular level. In this proof of concept Phase I study, we propose to use our cutting edge technology that combines the robust nature of the rabbit immune system with the power of yeast display technology to demonstrate the power of this approach to isolate highly specific, high affinity rabbit monoclonal antibodies against three derivatives of adenosine, inosine, N6-methyl-adenosine and N1-methyl-adenosine.
Emerging evidence has suggested that so-called RNA editing and base modification plays a critical role in enhancing the complexity of the central nervous system (CNS) response to developmental and environmental cues. However, while modern sequencing methods have indicated the widespread nature of these changes, their exact role in normal neurological function and in neurological disease remains poorly characterized, in large part because of the lack of tools with the necessary ability to distinguish between very closely related ribonucleosides with small molecular differences. In this project we propose to use our novel technology platform to isolate renewable monoclonal rabbit antibodies with the necessary affinity and high degree of specificity to distinguish such fine differences.