In the age of COVID-19, there has been a ton of scientific interest in nanobodies, or single-domain antibodies that can be used for finely targeted viral vaccines. It’s also been a hot topic among users of our BioXp™ system — an automated synthetic biology workstation which significantly accelerates processes involved in nanobody discovery and development.
In a recent webinar, Shruti Bakshi, a postdoctoral research scientist at the University of Oxford’s Jenner Institute, spoke about her team’s efforts to develop single-domain antibodies for use as oral vaccines. The BioXp™ system has been integral in streamlining that work. If you don’t have time to tune in for the whole presentation, here are a few highlights.
All eyes on nanobodies
Bakshi first introduced attendees to the various forms of antibodies used for therapy, showing where single-domain antibodies fit into the landscape. She noted that many large pharma companies and biotech firms are actively working on development programs for these antibody fragments. In fact, last year, Ablynx became the first company to receive FDA approval for a nanobody-based treatment. According to Bakshi, nanobodies offer several advantages: low immunogenicity, high stability, lower production costs, and varied delivery routes (including oral, nasal, and ocular).
The fusion element
While nanobodies alone have advantages, Bakshi said that combining them with albumin or other fusion elements can increase their half-life and have other positive effects on avidity and protection against isotype dependency. At Oxford, Bakshi and her colleagues have been working on fusion designs that would allow for better targeting in areas like the intestines, where uptake in mucosal membranes tends to be low. She described a project in which aminopeptidase N was used to create a fusion molecule with a nanobody. For this work, they perform cloning and production of these fusion nanobodies with the automated BioXp™ system to significantly reduce the turnaround time associated with these tedious manual assembly and cloning processes. “In just an overnight run, we had all of our constructs,” she said. Of 30 constructs produced and cloned into yeast, only one had an error. Implementing the BioXp™ system sped up the process, required less cloning overall, and eliminated the need for separate assembly steps.
The desired response
Functional testing showed that the fusion nanobodies bound as expected, even within intestinal cells, and induced the desired targeted immune response. “We found what we were looking for,” Bakshi said. She and her team plan to continue development of these and other fusion nanobody elements.
Learn more about antibody drug discovery using the BioXp™ system.