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The NC State Lab That Spent 40 Years Engineering a Better Probiotic

The NC State Lab That Spent 40 Years Engineering a Better Probiotic

Most supplements start with a marketing brief. A brand identifies a market, sources a generic formulation from a contract manufacturer, and builds a story around it after the fact. The science, if present at all, is borrowed — citations to studies done on other companies' products, loosely applied to what's inside the bottle.

CodonRX started differently. It started in a microbiology lab in 1985.

Four Decades of a Single Question

NC State University's Food Microbiology Lab has been studying Lactobacillus acidophilus — the most widely used probiotic species in the world — for over four decades. Long before probiotics became a consumer category, researchers at NC State were asking a foundational question: how, precisely, does L. acidophilus interact with the human gut?

That question led, over the years, to a detailed map of how the bacterium adheres to the gut epithelium, how it influences the mucosal immune environment, and how it communicates — through molecular signals — with the cells lining the gut wall. Much of what the supplement industry now claims generically about "L. acidophilus benefits" is traceable, at least in part, to the scientific foundation built at NC State over those decades.

It also led to a discovery that the industry has largely chosen to ignore.

A CRISPR Pioneer's Contribution to Probiotics

Prof. Rodolphe Barrangou, PhD

Chief Scientific Advisor, CodonRX  |  Distinguished Professor, NC State University

Inventor on the first CRISPR patent. Co-founder of Intellia Therapeutics (Nasdaq: NTLA). Former probiotics engineer at DuPont. Chairman, Caribou Biosciences. Professor, NC State Food, Bioprocessing and Nutrition Sciences. One of the most cited researchers in both CRISPR and probiotic biology.

Prof. Rodolphe Barrangou is best known in the broader scientific community as one of the architects of CRISPR — the gene-editing technology that has transformed medicine, agriculture, and biology. He holds the first CRISPR patent and co-founded Intellia Therapeutics, one of the leading CRISPR therapeutics companies. He chairs the CodonRX Scientific Advisory Board.

What's less widely known is that Barrangou spent years before his CRISPR work as a probiotics engineer — specifically working with L. acidophilus at NC State. That dual expertise — deep knowledge of probiotic biology and mastery of precision genetic tools — positioned him to ask a question that no one had seriously pursued: what if you could remove the harmful property of L. acidophilus without losing the beneficial ones?

The Discovery That Changed the Problem Statement

The harmful property in question is a molecule called lipoteichoic acid, or LTA. It sits on the outer cell wall of L. acidophilus — and every other gram-positive bacterium. LTA is not an accidental byproduct; it is a structural component of the cell wall, present on every live bacterial cell.

The problem is that the immune cells lining the human gut recognize LTA. Specifically, LTA binds to TLR2 — Toll-like receptor 2 — a pattern recognition receptor in the gut mucosa. TLR2 activation by LTA stimulates the production of pro-inflammatory cytokines including IL-12 and TNF-alpha. These cytokines are part of a normal immune surveillance response, but in people with IBS or other functional gut conditions, this inflammatory signaling can amplify the very symptoms — pain, cramping, urgency, bloating — that probiotics are supposed to address.

Research published in PNAS in 2011 established this mechanism directly and rigorously.1 The finding was striking: standard L. acidophilus, the "beneficial" probiotic in most major commercial products, activates the same inflammatory receptor pathway implicated in IBS symptom generation. The probiotic that millions of IBS sufferers were taking to feel better was, at a cellular level, stimulating the same pathway driving their discomfort.

The research showed that it wasn't L. acidophilus itself that was the problem — it was LTA, a single structural component of its cell wall. Remove LTA, and the inflammatory trigger disappears while the beneficial properties remain. — from the NC State research program on LTA-deficient Lactobacillus

The Engineering Solution: NCK2025™

Using genetic modification techniques developed and refined at NC State, the research team deleted the gene responsible for LTA biosynthesis. The result — designated NCK2025™ — is an L. acidophilus strain that:

  • Carries no LTA on its cell wall
  • Retains the superior gut epithelial adherence properties of wild-type L. acidophilus
  • Retains the mucosal and cytokine-modulating properties of L. acidophilus
  • Does not activate TLR2 in the manner that drives pro-inflammatory cytokine production

This was not a reformulation or a novel blend. It was a fundamental re-engineering of the bacterium itself — removing the one molecular component responsible for its inflammatory activity while preserving everything else. The research established this through careful comparison of the LTA-deficient strain against wild-type L. acidophilus in controlled studies of gut inflammation.

NCK2025™ is protected by two US patents — 9,340,792 and 9,980,992 — covering the strain and its application in gut health.2, 3

The Path to Market

  • 1985

    NC State Food Microbiology Lab begins foundational research on Lactobacillus acidophilus gut interactions.

  • 2011

    Landmark PNAS paper establishes LTA as the pro-inflammatory mechanism in standard L. acidophilus. NCK2025™ validated in research setting.

  • 2016–17

    US Patents 9,340,792 and 9,980,992 granted, protecting NCK2025™ and its therapeutic application.

  • 2022–23

    Kevin White, PhD (former President & CSO of Tempus AI) acquire the technology and found CodonRX. Prof. Barrangou joins as Chief Scientific Advisor.

  • 2024

    CodonRX | AI launches commercially. GMP manufactured in the US. First clinic partnerships established in the US and Singapore.

  • April 2026

    NC State publishes official article: "NC State Science to Supplement: CodonRX Pioneers a New Era in Gut Health" during IBS Awareness Month.4

What This Means for IBS Sufferers

The supplement industry is not short of claims. What it is short of is products built on independently published, peer-reviewed science with patent protection, a decades-long institutional research record, and a named scientist of Barrangou's stature on the advisory board.

CodonRX | AI is not a supplement industry formulation. It is a biotech product that spent the better part of forty years moving from scientific question to bench research to published validation to patent to commercial product. The mechanism is understood. The research is public. The intellectual property is protected.

The CodonRX | AI Scientific Foundation

  • 40+ years of NC State University L. acidophilus research
  • Peer-reviewed mechanism published in PNAS (2011)
  • Two US patents protecting NCK2025™ (9,340,792 and 9,980,992)
  • Chief Scientific Advisor: inventor on the first CRISPR patent, co-founder of Intellia Therapeutics
  • GMP manufactured in the USA; independently tested for potency and purity
  • Endorsed by NC State University Office of Research Commercialization (April 2026)

For IBS sufferers who have tried probiotic after probiotic without meaningful results, that foundation matters. The question was never whether L. acidophilus could support gut health. The question was whether the version of L. acidophilus available commercially was doing more harm than good by carrying LTA. Forty years of research at NC State produced a definitive answer — and a strain engineered around it.

Read the NC State research and learn more about the science behind NCK2025™.

References & Notes

  1. Mohamadzadeh M, et al. "Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid." Proceedings of the National Academy of Sciences (PNAS). 2011;108 Suppl 1:4623–30. Demonstrates the TLR2/LTA mechanism and validates NCK2025™ as a low-inflammation alternative to wild-type L. acidophilus.
  2. US Patent No. 9,340,792 — "Lipoteichoic acid deficient Lactobacillus acidophilus and uses thereof." USPTO.
  3. US Patent No. 9,980,992 — continuation/expanded claims on the NCK2025™ strain and applications. USPTO.
  4. NC State University Office of Research and Commercialization. "NC State Science to Supplement: CodonRX Pioneers a New Era in Gut Health." April 2026. Available at: research.ncsu.edu
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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