# Novel Nanoligomer-Based Therapeutics for Inflammatory Bowel Disease

> **NIH NIH R43** · SACHI BIOWORKS, INC. · 2023 · $55,000

## Abstract

PROJECT SUMMARY—Sachi Bioworks has developed a platform to rapidly generate Nanoligomers, a novel
family of nanoparticle-bound, modified nucleic acid oligomers that up- or down-regulate the expression of
selected proteins by binding to targeted DNA or mRNA. In preliminary work, Sachi demonstrated the ability to
selectively target and alter the expression of immunomodulatory proteins produced by > 30 human gut
anaerobes, which suggests Nanoligomers could be developed as a potential therapy for inflammatory bowel
disease (IBD) or other conditions promoted by inflammatory processes in the gut microbiota. In this Phase I
SBIR, Sachi proposes to apply this platform to rapidly design and build Nanoligomers to target Biosynthetic Gene
Clusters (BGCs) in gut microbial strains that produce immunomodulatory metabolites and then test these
Nanoligomers in vitro and in vivo to establish proof-of-concept to support further development as either a
standardized or personalized treatment for IBD. Aim 1. Design and build Nanoligomers to target BGCs in
six gut bacteria known to produce metabolites involved in anti-inflammatory or inflammatory processes
in the intestine. Based on the literature on IBD and gut microbiota, Sachi identified 14 metabolites of interest
encoded in BGCs in 6 species of bacteria (Table 3, Research Strategy). In this aim, Sachi will use the platform
to a) design and build Nanoligomers to target each of these BGCs, b) conduct in vitro assays to assess the ability
of each Nanoligomer to up- or down-regulate production of the target metabolite in the relevant bacteria, and c)
assess the immunomodulatory effects of lysates from Nanoligomer-treated bacteria on human peripheral blood
mononuclear cells (PBMCs). Milestones and Success Criteria: 1) Design, build, and test at least 42
Nanoligomers (three per metabolite) and 2) Select the two Nanoligomers from that group that produce the
greatest change in PBMC cytokine expression (thresholds: ≤ 50% of wild-type expression of pro-inflammatory
cytokines or ≥ 200% increase in anti-inflammatory cytokines). Exploratory: Characterize change in metabolite
production in response to Nanoligomer treatment. Aim 2. Characterize immunomodulatory and inflammatory
effects of the Nanoligomers in vivo. To assess the effects of the Nanoligomers on immunomodulation and
markers of inflammation and provide proof-of concept in the more complex setting of a live animal intestine,
Sachi will evaluate the effect of the top two Nanoligomers from Aim 1 and one missense Nanoligomer on the gut
microbiome and immune responses in mouse models of chronic colitis and genetic IBD. Sachi will assess the
effects on histology in colon tissue and cytokine production in the colon and blood. Milestones and Success
Criteria: Inhibitory Nanoligomers will produce ≥ 50% decrease in pro-inflammatory cytokines compared to
missense Nanoligomer and activating Nanoligomers will produce ≥ 200% increase in anti-inflammatory cytokines
compared to miss...

## Key facts

- **NIH application ID:** 10764688
- **Project number:** 3R43DK132980-01A1S1
- **Recipient organization:** SACHI BIOWORKS, INC.
- **Principal Investigator:** Prashant Nagpal
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2022-03-06 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764688

## Citation

> US National Institutes of Health, RePORTER application 10764688, Novel Nanoligomer-Based Therapeutics for Inflammatory Bowel Disease (3R43DK132980-01A1S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10764688. Licensed CC0.

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