# Epigenome Editing in Opioid Action

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $193,125

## Abstract

Project Summary
 The goal of this project is to develop CRISPR epigenome editing tools that achieve cell type specificity
and in some cases temporal specificity to target opioid regulated molecules. Opioid use, dependence, and
addiction have dramatically increased to epidemic proportions in recent years, leading to substantial
financial and societal health burdens, as well as an increasing number of overdoses. The number of
encounters with synthetic opioids, primarily fentanyl, has increased 300% since 2014, resulting in an
increase of 72% in synthetic opioid overdoses. To combat this epidemic it is imperative that we
understand the neurobiological underpinnings that lead to opioid use disorder. We must identify
disrupted neuron subtypes in the brain in opioid use disorders and dysregulated molecules within
these neurons that underlie cellular, circuit, and ultimately behavioral adaptations. We must then
develop more effective tools to target endogenous gene transcription of molecules disrupted in opioid
used disorder. To do this we performed RNA-seq in nucleus accumbens medium spiny neuron
subtypes, those expressing D1 or D2, in fentanyl abstinent animals, during a time point in which they
display stress vulnerable behavior. We identified key gene expression networks that are altered in
MSN subtypes of fentanyl abstinent mice.
 In this proposal we will develop CRISPR epigenome editing tools, including temporal specific
Optogenetic CRISPR tools, for selective cell subtype targeting of key fentanyl regulated genes in D1-
MSNs and D2-MSNs. We will test these tools in Neuro2a cells and then in vivo in MSN subtypes
(R21). Validated tools will be used in vivo to alter major hub genes, highly connected genes that
regulate expression of other genes within a network. RNA-seq on MSN subtypes during fentanyl
abstinence will determine if CRISPR tools are effective in targeting hub genes to alter their gene co-
expression networks (R33). In parallel we will test Opto-CRISPR tools to disrupt hub genes during
discreet stress susceptible and opioid intake and relapse time points (R33). Collectively, our studies
have the ability to uncover unique opioid molecular mechanisms by targeting the epigenome at
endogenous gene loci. Importantly our developed tools can be applied across all brain regions, cell
subtypes, and neuroscience disciplines.

## Key facts

- **NIH application ID:** 10071231
- **Project number:** 1R21DA052101-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mary Kay Lobo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071231

## Citation

> US National Institutes of Health, RePORTER application 10071231, Epigenome Editing in Opioid Action (1R21DA052101-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071231. Licensed CC0.

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