# Programmed Differentiation Circuits for Organoids using Meso-Microfluidics

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $601,284

## Abstract

We propose a new platform that leverages synthetic biology genetic circuits and micro/mesofluidic
instrumentation to rapidly advance the field of organoids. Specifically, we will genetically engineer self-
organizing tissues from human pluripotent stem cells into co-developed liver and pancreas organoids
possessing vascularization and other mature properties, such as adult level albumin production. The
application of synthetic biology to organoid development (programmable organoids) provides an exciting new
opportunity for engineering and testing of organoids encoding live cell sensors of cell state and for embedding
circuits that express cell-type and cell-state specific transcription factors. We will engineer novel microfluidic
and mesofluidic platforms to enable low cost and high throughput development and testing of programmable
organoids. Our hypothesis is that co-development of hiPSC-derived liver and pancreas provides cell-cell
interactions that contribute to vascularization and other important elements in organoid development that will
lead to mature organ formation. To test our hypothesis, we will genetically encode live-cell sensors to monitor
liver organoid develop, co-develop liver and pancreas organoids, and create genetic circuits that lead to
mature organoid formation. We will use synthetic classifier genetic circuits that evaluate changes in cell state in
real time, and generate relevant protein outputs for driving differentiation in a cell-type specific manner. This
these circuits will enable autonomous generation of new and improved versions of organoids, including mature
liver organoids and co-developed liver/pancreas organoids. Determining the precise spatiotemporal nature of
cell state transitions and the relevant transcription factors to drive differentiation is not only essential for
creating new and effective organoid developmental programs, but will also provide important scientific insights
to understanding the fine aspects of differentiation and co-development. Successful achievement of our aims
will have a broad impact in the areas of gene therapy, drug testing, and personalized medicine. For example,
the ability to co-develop matched organoid systems will enable patient-specific drug development (e.g. for
cancer therapy) that is more accurate than expensive and controversial alternatives, such as the use of
humanized mice. This work will also support the long-term goal of producing mature organoids and organ
systems suitable for transplantation.

## Key facts

- **NIH application ID:** 9896824
- **Project number:** 5R01EB025256-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** RON WEISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $601,284
- **Award type:** 5
- **Project period:** 2018-07-17 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896824

## Citation

> US National Institutes of Health, RePORTER application 9896824, Programmed Differentiation Circuits for Organoids using Meso-Microfluidics (5R01EB025256-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896824. Licensed CC0.

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