# Core C: Genome Engineering Core

> **NIH NIH P01** · J. DAVID GLADSTONE INSTITUTES · 2023 · $283,535

## Abstract

PROJECT SUMMARY/ABSTRACT
CORE C – GENOME ENGINEERING CORE
Core C is focused on providing the most up-to-date genome engineering technology for studies of cardiac
development. We will develop and adopt emerging technology for CRISPR/Cas9-mediated gene deletions,
single-base changes, transgene insertions, and epigenetic remodeling. The PPG proposal utilizes advanced
genome engineering techniques. We will specifically provide genome engineering services of human iPSCs to
efficiently deliver engineered iPSCs for cardiac differentiation. The Genome Engineering Core will also
provide epigenome editing methods, that modify the cell's genome without cutting DNA. The CRISPR-
associated nuclease (Cas9) has been modified so that the nuclease is inactive in making “dCas” that can now
be used to carry and localize a wide variety of bioactive molecules to any location in the genome. We
pioneered the use of CRISPRi that silences gene expression in iPSCs, and are involved in developing better
methods that activate gene expression (CRISPRa).
 Our team is an established leader in genome engineering, and has made efforts to improve every aspect of
genome editing in human iPSCs to benefit the PPG investigators in their efforts to unravel the molecular basis
of congenital heart disease. In the last 5 years, we made >50 different genetically modified human iPSC lines
with point mutations that exactly mimic the disease mutations, generate insertions/deletions (indels) for gene
knockouts, or introduce endogenous gene tags for molecular studies of protein function (Miyaoka et al., 2014,
Huebsch et al., 2015, Mandegar et al., 2016, Judge et al., 2017). The Genome Engineering Core will adopt
the latest methods for genome engineering, such as the use of CRISPR/Cas9 RNP-protein complexes (RNP)
to introduce insertion/deletions (indels), or delete discrete portions of genes to inactivate them in iPSCs as well
as in iPSC-derived cardiomyocytes, since RNP-mediated genome editing is more efficient and accurate in our
experience. In addition, the Genome Engineering Core will provide genome engineering services for the
insertion of transgenes at endogenous loci, as well as develop new CRISPR methods for the PPG
investigators to further investigate the cardiac interactome. The Genome Engineering Core will develop a
pipeline to deliver high-quality engineered iPSCs to the PPG projects with continuously updated techniques, to
answer vital questions in heart development.

## Key facts

- **NIH application ID:** 10692601
- **Project number:** 5P01HL146366-05
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Bruce R Conklin
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $283,535
- **Award type:** 5
- **Project period:** 2019-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692601

## Citation

> US National Institutes of Health, RePORTER application 10692601, Core C: Genome Engineering Core (5P01HL146366-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10692601. Licensed CC0.

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