# Custom-engineering a 3D brain organoid platform to model viral infections of the central nervous system

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2021 · $299,833

## Abstract

SUMMARY – Project 1
Despite the tremendous promise of cerebral organoid technology for studying human brain development,
modeling brain diseases and testing drug efficacy, we are still at the beginning of an era to engineer mini-
brains from human stem cells. For broad applications in basic and translational research, organoid
development should be scalable, cost efficient and highly consistent. Previous methods are largely based on
cell self-assembly with little external control, and organoids generated by this approach exhibit large variability
from sample to sample. We recently developed a miniaturized bioreactor and a protocol to generate forebrain-
specific organoids from human iPSCs. These organoids recapitulate key features of human cortical
development, including progenitor zone organization, neurogenesis, and gene expression. We employed the
forebrain organoid platform to model Zika virus (ZIKV) exposure and showed that preferential, productive
infection of neural progenitors by ZIKV leads to increased cell death and reduced proliferation, resulting in
decreased neuronal cell-layer volume resembling microcephaly. In this collaborative research Center, we will
investigate the effects of ZIKV and West Nile virus infections at different time points of organoid development
to evaluate our platform with two different neurotropic flaviviruses that may target different stages of neural
development. Project 1 will focus on technology development to reduce organoid heterogeneity and allow for
quantitative analyses of the effects of different viruses on organoid development. To model later stages of
brain development, we will adopt state-of-the-art bioengineering approaches to improve the diffusion of media
to the organoids and reconstitution of different cell types. And finally, we will develop a medium-throughput
platform for compound testing and perform a pilot assay using compounds with known biological effects on
viral-infected cells.

## Key facts

- **NIH application ID:** 10134222
- **Project number:** 5U19AI131130-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Guo-li Ming
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,833
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134222

## Citation

> US National Institutes of Health, RePORTER application 10134222, Custom-engineering a 3D brain organoid platform to model viral infections of the central nervous system (5U19AI131130-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134222. Licensed CC0.

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