SPLTRAK Abstract Submission
Paving a path towards single olfactory receptor activation using synthetic aptamers
Shani Agron1, Shireen Fseisy2, Itai Rusinek2, Gil Loewenthal2, Ido Bachelet2, Noam Sobel1
1Weizmann Institute of Science, Rehovot, , Israel
2Augmanity ltd., Rehovot, , Israel

Our nose allows us to detect and discriminate between a vast range of structurally diverse odorants thanks to millions of olfactory receptors (ORs) of about 400 different types.  Each OR may react to a repertoire of different odorants and each odorant can activate more than one type of OR, this constitutes a highly complexed combinatorial code that results in odor perception. The contribution of a given olfactory receptor to olfactory perception remains unknown. A potentially helpful key to this riddle would be a synthetic agonist for a single OR type. Aptamers are short single stranded oligonucleotide sequences (DNA, RNA, or synthetic analogs of the two) that can fold into stable 3D structures and bind to different targets with high affinity and specificity. Exploiting these advantages, we selected aptamers to olfactory receptor 1A1 (OR1A1) using systematic evolution of ligands by exponential enrichment (SELEX) technique on cells that express the receptor. To gain specificity we introduced a negative selection step at an early stage of the SELEX using the same type of cells with no OR1A1 expression. Using a novel approach, we have selected aptamers that specifically bind to OR1A1. This is the result of two independent selection procedures, one was done in the presence of dihydrojasmone, a known odorant for OR1A1 and the second with no odor presence. A repertoire of aptamers towards the odor bound and unbound forms of the receptor may shed some light on the areas involved in odor binding by ORs. Additionally, we are currently testing rather these aptamers can modulate the receptor activity and to induce or alter odor perception.