# New Chromatin Insulators and Enhancers for Gene Therapy of the Hemoglobinopathies

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $580,093

## Abstract

ABSTRACT
 The goals of this project are to use genomic approaches to identify, in the human genome,
powerful chromatin insulators and powerful erythroid specific enhancers. Use of powerful
insulators in therapeutic gene therapy vectors will increase safety by decreasing the risks of
vector-related genotoxicity. Availability of powerful erythroid specific enhancers will increase the
efficacy of gene therapy in patients with severe thalassemia.
 With the studies of the first specific aim we will discover powerful chromatin insulators in the
human genome using the novel genomic screening approaches we have developed. Special
emphasis will be given in identifying powerful barrier insulators which also possess powerful
enhancer blocking activity. Such insulators are expected to improve both the safety and the
efficacy of integrating gene therapy vectors. We will determine the structural characteristics of
the new insulators and we will investigate the structural basis of the variation in their potency.
 In specific aim 2 we will discover new powerful erythroid specific enhancers in the human
genome using molecular and informatics methods. We will verify the erythroid lineage specificity
of the new enhancers, we will characterize them and will use them to identify the molecular
features that determine erythroid lineage specificity.
 With the studies of Specific Aim 3 we will produce a new generation of globin gene therapy
vectors. The most powerful insulators of Specific aim 1 will be used to determine the optimal
sizes, the highest titers and the highest protection from genotoxicity required for the gene
therapy vectors. The most powerful enhancers of Specific Aim 2 or enhancer cassettes will be
used for quantitative assessments of their potency in supporting globin gene expression. The
best insulators and enhancers will be incorporated in globin gene vectors and their therapeutic
potency will be assessed ex vivo in the erythroid cells of thalassemic patients and in vivo in
thalassemic mice.

## Key facts

- **NIH application ID:** 9926304
- **Project number:** 5R01HL136375-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** THALIA STAMATOYANNOPOULOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $580,093
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926304

## Citation

> US National Institutes of Health, RePORTER application 9926304, New Chromatin Insulators and Enhancers for Gene Therapy of the Hemoglobinopathies (5R01HL136375-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9926304. Licensed CC0.

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