# Engineering a human brain organoid-based platform to study neurotropic viruses

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2021 · $1,499,160

## Abstract

SUMMARY – Overview
 Modeling of infectious diseases that affect the human central nervous system (CNS), such as those
associated with Zika virus (ZIKV) and West Nile virus (WNV), has been challenging due to the inaccessibility of
the relevant cell types. Reprogramming human somatic cells, such as skin fibroblasts, into induced pluripotent
stem cells (iPSCs) provides a genetically tractable and renewable source of human neural cell populations. We
can differentiate these iPSCs into many of the cell types critical for the study of neurotropic viruses, but
typically this is performed in monolayer cultures to allow for more control and to generate more homogeneous
cell populations, but this methodology lacks the self-organizing properties and interactive dynamics among
different cell populations observed during organ development. Recently, more complex structures resembling
whole developing organs, named organoids, have been generated from human iPSCs via 3D culturing
methods. This emerging new technology has the potential to significantly advance our understanding of
infectious diseases and for future therapeutic development. The success of this approach, however, critically
depends on how well organoids mimic biological structures, recapitulate human physiology and disease
pathology, and incorporate components critical to disease and human host responses. We propose to develop
a robust platform for organoid development to model brain development that can be adopted by single labs for
basic research, and is amenable to translational studies and drug development and testing.
 Our Research Center is comprised of three Research Projects, a Scientific Core, and an Administrative
Core led by experts in virology, stem cell biology, neural development, and bioengineering. We will focus on
ZIKV and WNV, two neurotropic flaviviruses, to develop our organoid platform, which can then be used by the
scientific community to investigate other infectious diseases that affect the nervous system. Importantly, ZIKV
and WNV are thought to impact the CNS at different stages of development, with ZIKV having been recently
implicated as being causal for microcephaly in some pregnant women. This affords us the opportunity to
develop an organoid platform with proof-of-principle testing with viruses suspected to have cell type- and
stage-specific tropism. Project 1 will focus on technology development to generate more mature organoids
and the scaling up of robust assays to perform medium-throughput compound testing. Project 2 will focus on
ZIKV infections in early stage organoids and Project 3 will evaluate co-culture organoid systems to model
WNV infections in later stage organoids. The projects will be supported by a Scientific Core that will provide
cells and on-site training to Projects 2 & 3, as well as optimization of differentiation protocols and
bioinformatics analyses. Finally, the Administrative Core will provide logistical support to facilitate
collaborations amon...

## Key facts

- **NIH application ID:** 10134216
- **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:** $1,499,160
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134216

## Citation

> US National Institutes of Health, RePORTER application 10134216, Engineering a human brain organoid-based platform to study neurotropic viruses (5U19AI131130-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134216. Licensed CC0.

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