Engineered commensals for targeted nose-to-brain drug delivery.

Intranasal administration through the olfactory epithelium (OE) presents a direct pathway for brain-targeted therapeutic delivery, although its feasibility is hampered by the anatomical and absorptive limitations of the OE. In this study, we identified Lactobacillus plantarum WCFS1 (Lp), a commensal strain with a natural affinity for the OE and engineered it to function as a vector for cerebral drug delivery. Upon intranasal administration, Lp released specific payload molecules within the OE, with subsequent transport and accumulation in the brain. The therapeutic efficacy of Lp was further validated by the recombinant production and secretion of appetite-regulating hormones. When administered intranasally in a murine model of obesity prevention, the engineered Lp significantly alleviated obesity-related symptoms. This was evidenced by decreased appetite, reduced body weight gain, and improved glucose metabolism and fat mass deposition. Our study demonstrates the capability of Lp as an intranasal delivery vehicle, emphasizing its potential for brain-targeted therapeutic applications.

• Publication year

  2025

• Venue

  Cell

• Publication date

  2025-02-01

• Fields of study

  Medicine, Engineering

• Identifiers
  DOI 10.1016/j.cell.2025.01.017PMID 39914382
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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