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Generation of functional organs and tissues using organism interspecific blastocyst complementation

Award Number: DP1DK113616
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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¿PROJECT SUMMARY: In vitro differentiation of cultured pluripotent stem cells (PSCs) provides a promising tool for the generation of specific cell types useful for cell replacement therapies. Despite rapid progress over the last decade, numerous challenges encompassing cell-production quantity, quality and safety remain to be addressed before full-fledged clinical application becomes a reality. Moreover, generation of functional organs from cultured PSCs, a much needed breakthrough to meet the rising demands for organ donors, remains improbable. This is largely due to our limited understanding of molecular and genetic processes underlying in vivo tissue/organ generation, which has been perfected through millions of years’ evolution. Nature has evolved a sophisticated and robust system to generate functional tissues and organs during normal course of embryo development. The intrinsic genetic program works seamlessly with extrinsic developmental niches in a perfect spatiotemporal manner to enable embryonic cells to commit to specific cell lineages and be organized into higher-order tissue architectures. Blastocyst complementation is based on emptying these developmental niches created by knocking out gene(s) critical for the specific tissue/organ development and use donor chimeric-competent PSCs to colonize the vacant niche and generate desired tissues/organs of donor origin. With the booming of CRISPR/CAS9-mediated genome engineering gene knockout animals can be generated with high efficiency by co-injection of Cas9 mRNA and gRNAs directly into zygotes. Also, chimeric-competent primate PSCs have seen several promising developments very recently. By combining the strength of zygote genome editing and chimeric-competent primate PSCs, we propose to establish a novel interspecific blastocyst complementation system for the generation of functional organs in a large animal host, the pig. For this first study, we will focus on using PSCs derived from non-human primate species, to evaluate the efficacy and safety of our proposed strategy. Our study will provide critical information for future application into humans. If successful, this approach will lead to a paradigm shift in regenerative medicine and will help to overcome the shortage of organ donors.


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: 2023 ( Subtotal = -$196,902 )
2023	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	12/6/2022	SUPPLEMENT FOR EXPANSION	-$65,272
2023	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	5	12/6/2022	NON-COMPETING CONTINUATION	-$131,630
														Subtotal = -$196,902

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	5	10/26/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,451,000 )
2020	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/27/2020	SUPPLEMENT FOR EXPANSION	$481,000
2020	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	5	8/26/2020	NON-COMPETING CONTINUATION	$970,000
														Subtotal = $1,451,000

Issue Date FY: 2019 ( Subtotal = $970,000 )
2019	2019	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	4	9/4/2019	NON-COMPETING CONTINUATION	$970,000
														Subtotal = $970,000

Issue Date FY: 2018 ( Subtotal = $970,000 )
2018	2018	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	3	9/7/2018	NON-COMPETING CONTINUATION	$970,000
														Subtotal = $970,000

Issue Date FY: 2017 ( Subtotal = $970,000 )
2017	2017	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	2	8/25/2017	NON-COMPETING CONTINUATION	$970,000
														Subtotal = $970,000

Issue Date FY: 2016 ( Subtotal = $970,000 )
2016	2016	SALK INSTITUTE FOR BIOLOGICAL STUDIES	P.O. BOX 85800	SAN DIEGO	CA	92186	SAN DIEGO	USA	Trans-NIH Research Support	000	1	9/28/2016	NEW	$970,000
														Subtotal = $970,000

Grand Total All Awards = $5,134,098

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Generation of functional organs and tissues using organism interspecific blastocyst complementation

Award Number: DP1DK113616

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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