Friday, April 26, 2024 4/26/2024

Multicell type human liver on chip microphysiological platform to examine CRISPR based gene modulation

Award Number: U01EB029372
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Genome engineering technology has the capability of resolving many unmet needs in the field of gene therapy. Among the newly developed genome engineering tools, the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) System has revolutionized genome editing due to ease of engineering and programmability. Despite its tremendous potential, CRISPR for gene therapies faces several challenges. To be successful, CRISPR must be specific and have minimal off-target effects both in genome and cells/tissues. As such, precise detection of off-target effects on the genomic loci is another important factor that has received considerable attention so far. Efficient translation of CRISPR to human trials requires human-based platforms that can provide direct information about the biological consequences of genome editing. Most studies so far have been conducted in cell lines or animal models. Little progress has been made to examine the gene editors in platforms that can yield human relevant readouts and enable us to rapidly assess and predict adverse effects of CRISPR in physiologically relevant human models. Human organ on-a-chip platforms can facilitate studies on the safety of genome editing technologies and delivery systems in human. We hypothesize that human liver on a chip can be adopted for accurate assessment of toxicity and off-target activity of CRISPR-based gene editing ex vivo. In aim 1 we will investigate cellular innate response to Cas9 protein or gRNA in a complex human liver on a chip platform: We hypothesize that human liver on a chip platform can be employed to accurately predict cellular stress response to Cas9 protein, gRNA or delivery vehicles in primary human liver cells. In aim 2 we will examine CRISPR off-target activity in primary human liver cells within liver on a chip: We hypothesize that our human liver on a chip platform can be used to examine CRISPR off target cleavage in primary liver cells ex-vivo. Using a library of clinically relevant liver genes and designed gRNAs with different specificities, we will investigate CRISPR off-target activity and verify a set of transcriptomic or secretory factors in liver tissue that can serve as future markers for evaluation of CRISPR off target activity. In aim 3, we will understand the role of micro-environmental cues in CRISPR adverse effect on human liver cells in a chip. We will test the impact of mechanically non-rigid hydrogel-based scaffolds and low-grade inflammatory conditions in CRISPR gene editing efficiency in human tissue formed ex vivo.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = -$139,475 )
2020	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	004	2	9/2/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$180,090
2020	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	008	2	9/14/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$166,036
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	005	3	9/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$180,091
2020	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	002	2	6/25/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$355,633
2020	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	000	2	4/21/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$372,622
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	001	3	4/22/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$386,819
2020	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	006	2	9/4/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$201,962
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	003	3	6/25/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$355,633
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	007	3	9/4/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$355,633
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Research Support	009	3	9/14/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$166,036
														Subtotal = -$139,475

Issue Date FY: 2019 ( Subtotal = $574,584 )
2019	2019	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Trans-NIH Research Support	000	2	8/27/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$574,584
														Subtotal = $574,584

Grand Total All Awards = $435,109

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Multicell type human liver on chip microphysiological platform to examine CRISPR based gene modulation

Award Number: U01EB029372

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer