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CMCC 2339

Innovative Uses of Biofilms for Protein Delivery, Vaccine Development, and Infectious Disease Treatment

Inventors: Paula Watnick

Categories: Therapeutics

SubCategories: Gastrointestinal/Nutrition, Immunology, Infectious Disease

Keywords: Drug Delivery

Invention Description:

A biofilm is a microbial community attached to various biological or non-biological surfaces and is held in place by an extracellular matrix. Biofilms are implicated in many disorders of human health, and a deeper understanding of biofilms may allow them to be engineered for biomedical applications.

The lab of Dr. Paula Watnick, MD, PhD, at Boston Children’s Hospital has developed an innovative use of biofilms as a flexible platform for protein delivery and vaccine development. The researchers showed that functional enzymes can be fused to Bap1, RbmA and RbmC, three proteins in the biofilm extracellular matrix. In this way, researchers were able to utilize biofilms to present and concentrate proteins and antigens at various biotic and abiotic surfaces. Currently, this technique is being used to develop an improved whole-cell, oral cholera vaccine. A similar technique could be used in drug delivery. Small molecule or protein therapeutics could potentially be conjugated to Bap1, RbmA or RbmC to promote delivery to biofilm infection sites in the body.

The Watnick lab additionally studied the molecular composition of biofilms in order to give new insights into how biofilms can be disrupted in disease treatment. Researchers identified a peptide fragment produced by the proteolytic enzymes HAP, PrtV and VC0157, and they further showed that this fragment recruits additional bacteria to the biofilm surface. This finding suggests that novel inhibitors targeting HAP, PrtV or VC0157 could be developed to help block biofilm expansion.

Applications:

Vaccine development
• A platform that utilizes bacterial biofilms as a means for presenting and concentrating antigens at surfaces for vaccine development

Therapeutics delivery
• A platform to deliver therapeutics directly to the site of V. cholera infections in the GI tract; Therapeutic enzymes or small molecules can be conjugated to or targeted toward Bap1, RbmA or RbmC and delivered to biofilms
• Delivery of enzyme therapeutics directly to the site of other biofilm infections via intravenous or intramuscular routes by fusing the enzymes of interest to Bap1, RbmA or RbmC

Biofilm disruption
• Development of pharmacological inhibitors of HAP, PrtV and VC0157 to block recruitment of additional bacteria to existing biofilms. Such inhibitors could be used to treat patient infections or to disinfect surfaces

Competitive Advantages:

• Enables targeted delivery of proteins to biotic and abiotic surfaces through an inexpensive, genetically tractable model • Genetic approach to overexpress matrix-conjugated enzymes in V. cholera is self-renewing, as opposed to biochemical or in vitro methods
• Provides flexibility to genetically conjugate single or multiple antigens of interest to Bap1, RbmA or RbmC for the purpose of vaccine development. • By using multiple antigens in this vaccine-development platform, this technology could enable generation of vaccines with broader specificity and the ability to protect against multiple diseases at once.
• Has potential to improve the protective coverage of vaccines with minimal changes to cost, administration and storage

Business Opportunity:

• Non-exclusive license or exclusive license by field or sponsored research opportunity

Key Publications: Absalon C, Van Dellen K, Watnick PI (2011) A Communal Bacterial Adhesin Anchors Biofilm and Bystander Cells to Surfaces. PLoS Pathog 7(8): e1002210. doi:10.1371/journal.ppat.1002210.

Absalon C, Ymele-Leki P, Watnick PI, 2012. The Bacterial Biofilm Matrix as a Platform for Protein Delivery. mBio 3(4): doi:10.1128/mBio.00127-12. Smith DR, Maestre-Reyna M, Lee G, Gerard H, Wang AHJ, Watnick PI (2015) In Situ Proteolysis of the Vibrio Cholerae Matrix Protein RbmA Promotes Biofilm Recruitment. PNAS 112 (33): doi:10.1073/pnas.1512424112.

Absalon C, Ymele-Leki P, Watnick PI, 2012. The Bacterial Biofilm Matrix as a Platform for Protein Delivery. mBio 3(4): doi:10.1128/mBio.00127-12.

IPStatus: Pat. Pend.

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