Typical traditional probiotics lactobacilli and bifidobacteria are gaining great interest to be developed as living diagnostics and therapeutics for improving human health. However, the mechanistic basis underlying their inherent health beneficial property remain incompletely understood which can slow down the translational pipeline in the functional food and pharmaceutical field. Efficient genome editing will advance the understanding of the molecular mechanism of the probiotics' physiological properties and their interaction with the host and the host microbiota, thereby further promote the development of next-generation designer probiotics with improved robustness and tailored functionalities. With the expansion of genome editing strategies such as CRISPR-Cas-based tools and IPSD assisted genome engineering as well as other synthetic biology technologies, the research and application of these health-promoting bacteria for the food and pharmaceutical industry will be further enhanced.
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http://dx.doi.org/10.1016/j.copbio.2020.12.015 | DOI Listing |
Nat Med
January 2025
Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.
View Article and Find Full Text PDFNat Metab
January 2025
Department of Bioengineering, University of California, University of California, San Diego, La Jolla, CA, USA.
The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.
View Article and Find Full Text PDFNat Genet
January 2025
The Applied Plant Genomics Laboratory of Crop Genomics and Bioinformatics Centre and State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, Nanjing Agricultural University, Nanjing, China.
Ambiguity about whether the histidine-rich calcium-binding protein-coding gene (His) or the pore-forming toxin-like gene (PFT) or both are responsible for Fusarium head blight (FHB) resistance conferred by the Fhb1 quantitative trait locus hinders progress toward elucidating Fhb1 resistance mechanisms. Here, with a series of developed lines with or without PFT but all possessing His and five His-carrying PFT mutant lines created via gene editing, we show that PFT does not confer FHB resistance and that the His resistance effect does not require PFT in the tested conditions. We also show that PFT mutations are not associated with morphological and phenological characteristics that often affect FHB severity.
View Article and Find Full Text PDFNat Genet
January 2025
State Key Laboratory of Plant Environmental Resilience, College of Life Sciences, Zhejiang University, Hangzhou, China.
Rice production is facing substantial threats from global warming associated with extreme temperatures. Here we report that modifying a heat stress-induced negative regulator, a negative regulator of thermotolerance 1 (NAT1), increases wax deposition and enhances thermotolerance in rice. We demonstrated that the C2H2 family transcription factor NAT1 directly inhibits bHLH110 expression, and bHLH110 directly promotes the expression of wax biosynthetic genes CER1/CER1L under heat stress conditions.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Physiology, Korea University College of Medicine, Seoul, Republic of Korea.
With recent advancements in gene editing technology using the CRISPR/Cas system, there is a demand for more effective gene editors. A key factor facilitating efficient gene editing is effective CRISPR delivery into cells, which is known to be associated with the size of the CRISPR system. Accordingly, compact CRISPR-Cas systems derived from various strains are discovered, among which Un1Cas12f1 is 2.
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