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Multigene knockdown in Mycobacterium tuberculosis by repurposing the endogenous type III CRISPR system

Award Number: R03AI131223
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT The manipulation of gene expression in Mycobacterium tuberculosis (Mtb) remains a challenge. In particular the regulation of multiple genes simultaneously is difficult and prohibitively time consuming. The CRISPR-Cas system is an RNA-guided bacterial adaptive immune system with transformative potential for gene editing, and CRISPR interference (CRISPRi), is a new tool to control gene expression in many organisms. CRISPR systems are inherently multi-gene regulatory systems, based on their ability to express and process a CRISPR array into many dozen RNAs that can each target a different gene. This unique multi-gene targeting function has not yet been exploited because not all required precursor RNA processing components are known for most systems, precluding their heterologous expression. However, these limitations apply only to the orthogonal use of CRISPR systems when heterologous expression of all components is required. Endogenous CRISPR systems, in contrast, provide all necessary components for processing and interference and are optimally tuned to function in their particular host. Here, we will repurpose the endogenous Mtb type III CRISPR system for the regulation of genes in any strain and for multi-gene regulation.


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: 2019 ( Subtotal = -$3,263 )
2019	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	11/28/2018	NON-COMPETING CONTINUATION	-$27,467
2019	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	005	3	4/30/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$21,371
2019	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	004	2	4/30/2019	NON-COMPETING CONTINUATION	-$21,371
2019	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	006	3	6/5/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$2,991
2019	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	002	2	1/17/2019	NON-COMPETING CONTINUATION	$20,548
2019	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	003	3	1/17/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$20,820
2019	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Allergy and Infectious Diseases Research	001	3	11/28/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$27,467
														Subtotal = -$3,263

Issue Date FY: 2018 ( Subtotal = $98,000 )
2018	2018	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	2	12/20/2017	NON-COMPETING CONTINUATION	$98,000
														Subtotal = $98,000

Issue Date FY: 2017 ( Subtotal = $98,000 )
2017	2017	SEATTLE BIOMEDICAL RESEARCH INSTITUTE	307 WESTLAKE AVE N STE 500	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	12/30/2016	NEW	$98,000
														Subtotal = $98,000

Grand Total All Awards = $192,737

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Multigene knockdown in Mycobacterium tuberculosis by repurposing the endogenous type III CRISPR system

Award Number: R03AI131223

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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