Plasmid vectors for in vivo selection-free use with the probiotic E. coli Nissle

Background:

Inflammatory Bowel Diseases (IBD), including Crohn's disease and ulcerative colitis, are common, debilitating, and poorly treated conditions, affecting around eight million people worldwide. Current therapeutics include immunosuppressants and biologics that are often administered systemically. More than one-third of patients require surgical colectomy. These treatment options may reduce symptoms temporarily but even in the state of clinical remission, patients still have disease activity (e.g., inflammation) leading to relapse after a while. Complete remission happens when there are no symptoms and no disease activity in endoscopy or biopsy. Recently, it has been revealed that healing of the mucosal layer of digestive tracts can lead to longer and more permanent therapeutic outcomes. However, getting to that point is still a challenge. For instance, it is difficult to maintain a steady amount of drug at the site of disease, due to the constant flow of material through the gut. Therefore, new tools should be developed to address current limitations.

Technical Overview:

A Northeastern lab has invented an oral live biotherapeutic patch for the treatment of wounds in the gut. The patch consists of engineered bacteria that secret therapeutic proteins with anti-inflammatory properties directly into the diseased sites. The presence of bacteria as well as secreted proteins improve gut barrier function and leads to faster mucosal healing. This patch platform can be utilized to apply partners' drugs such as biologics (e.g., anti-TNFs, anti-interleukins, anti-integrins) into lesions for greater efficacy with fewer systemic side effects. The bacterial platform has a complete safety profile since it is made of an engineered strain of non-pathogenic E. coli. Bacteria multiply inside the gut, maintaining a relatively steady concentration over time, while secreting therapeutics directly at the site of disease. This strain of bacteria is engineered in a way to remain stable in the absence of antibiotic selection, which facilitates its use in vivo, and contributes to better performance as living gut therapeutics.

Benefits:

  • No need for systemic delivery (oral delivery)
  • High safety profile
  • Fast and efficient design of engineered strain of bacteria
  • Complete remission of disease symptoms
  • Fewer systemic side effects compared to other biologics
  • Maintaining a steady amount of drug in the site of disease
  • Simultaneous delivery of other biotherapeutics

Application:

  • Mucosal healing in IBD diseases
  • Delivering therapies to the gut

Opportunity:

  • Licensing
  • Collaboration
  • Commercial Partner
  • Development Partner
Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
PLASMID VECTORS FOR IN VIVO SELECTION FREE USE WITH THE PROBIOTIC E COLI NISSLE National *United States of America 18/026,439   3/15/2023     Published
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