Higashide, Wendy | Search NASA

DOE OSTI2022

Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display

The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.

SARS-CoV-2↗

DOE OSTI2018

Bio-Oxo Technology

Easel Biotechnologies, LLC’s Bio-Oxo process has demonstrated that isobutyraldehyde can be biologically produced from corn stover hydrolysate up to 56 g/L in a 14L fermentor. This was accomplished by metabolically engineering bacterial strains to not only produce isobutyraldehyde, but to do so by co-utilizing corn stover hydrolysate sugars, glucose and xylose. Also essential to the success of the Bio-Oxo process was that it utilized gas stripping as a means of product separation, allowing for the continuous removal of isobutyraldehyde. This aided in not only reducing energy costs associated with separation, but also alleviating product toxicity, resulting in higher production. Although we were not able to complete our economic analysis based on pilot scale fermentations, the improvements we have made from strain engineering to product separation, should result in the reduced cost of isobutyraldehyde. Still, as the project has ended prematurely, there is room for additional optimization. Improvements in productivity and sugar utilization would result in a further reduction in capital and recovery costs. As a biological-based process, the utilization of corn stover results in reduced greenhouse gas emissions as compared to petroleum-based chemical synthesis. In addition, as a true replacement chemical “drop in” system, no downstream production units need to be changed. Jobs can also be created as farm waste needs to be collected and transported to the new production facility.

09 BIOMASS FUELS↗