Novel approaches to detect and treat sepsis

Project Summary/Abstract:
Background. Sepsis, a severe and life-threatening condition, is one of the most common causes of death in
hospitalized patients. Sepsis is generally caused by bacterial infection, including both Gram-negative and
positive bacteria. In the United States, the hospital mortality rate of patients with sepsis could be as high as
41.1%, which accounts for more than 250,000 deaths and $20 billion loss annually. Due to the inadequate
sensitivity and specificity of the current technologies, there is no global standard for sepsis diagnosis. In this
project, the PI has the ambition to address the critical bottlenecks specifically of concern in sepsis testing using:
1) hybrid bio-inorganic nanobots, 2) CRISPR-based devices, and 3) CRISPR-equipped engineered phages.
Goals for the next five years. Our first goal is to engineer phage M13 with nanobodies on the capsid protein
pVIII and his-tags on the tail fiber protein pIII. After binding cobalt-coated magnetic nanoparticles, the resulting
hybrid bio-inorganic nanobots will be used to concentrate and purify pathogens from blood samples. Capture
efficiency will be investigated using spiked samples and then proceed to clinical ones. Taking advantage of
CRISPR and microfluidic technologies, the second goal is to fabricate portable devices to detect sepsis-related
pathogens, which can be used in resource-limited settings. The last goal is to engineer phages with different
CRISPR systems, that can be used to detect and combat sepsis-related bacterial pathogens. Towards the end
of the fifth year, we will have integrated these technologies as a robust tool for sepsis diagnosis.
Overall vision of the research program. The technologies we are developing will have a broad impact on the
biomedical research communities to detect and treat sepsis, even for other diseases. Our developed
technologies can also advance pathogen detection in other fields, such as food safety and environmental
monitoring.

Grant Number: 5R35GM147069-05
NIH Institute/Center: NIH
Principal Investigator: Juhong Chen