Discovery (Lead Identification)
Bacterial spores can be modified to display molecules of interest, including drugs, immunogenic peptides, antibodies and other functional proteins of interest (such as enzymes). The resulting engineered bacterial spores can provide many useful functions such as the treatment of infections, use as an adjuvant for the delivery of vaccines, and the enzymatic degradation of environmental pollutants.
Researchers at the National Cancer Institute’s (NCI) Laboratory of Molecular Biology have developed a novel, synthetic spore husk-encased lipid bilayer (SSHEL) particle that is uniquely suited for a variety of these functions. The assembly of SSHELs involves the insertion of the bacterial spore coat protein SpoVM into a lipid bilayer that is located on a synthetic core particle. SpoVM serves as a structural element and recruitment factor for the bacterial spore coat protein SpoIVA. When SpoIVA is conjugated to streptavidin, the SSHEL can bind to another molecule through a biotin linkage. This leads to the creation of a specialized SSHEL that can serve a particular biological function. The lab's pre-clinical work has demonstrated that SSHELs loaded with Doxorubicin reduced the tumor burden in a mouse tumor xenograft model of HER2-positive ovarian cancer. By varying the ratio of streptavidin-conjugated and unconjugated SpoIVA protein used in the manufacture of the SSHEL, it is possible to tailor the amount of functional molecule that is present in the SSHEL. This affords greater control over the level of activity that is provided by the SSHEL, thereby allowing the fine tuning of its function.