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Integrated particle image velocimetry and fluid-structure interaction analysis for patient-specific abdominal aortic aneurysm studies.
Biomed Eng Online
December 2023
Institute of Biomedical Engineering, Boğaziçi University, Kandilli Campus, Feza Gürsey Bld., Çengelköy, 34685, Istanbul, Turkey.
Background: Understanding the hemodynamics of an abdominal aortic aneurysm (AAA) is crucial for risk assessment and treatment planning. This study introduces a low-cost, patient-specific in vitro AAA model to investigate hemodynamics using particle image velocimetry (PIV) and flow-simulating circuit, validated through fluid-structure interaction (FSI) simulations.
Methods: In this study, 3D printing was employed to manufacture a flexible patient-specific AAA phantom using a lost-core casting technique.
Fabrication of deformable patient-specific AAA models by material casting techniques.
Front Cardiovasc Med
September 2023
BioCardioLab, Bioengineering Unit - Heart Hospital, Fondazione Toscana "G. Monasterio", Massa, Italy.
Background: Abdominal Aortic Aneurysm (AAA) is a balloon-like dilatation that can be life-threatening if not treated. Fabricating patient-specific AAA models can be beneficial for investigations of hemodynamics, as well as for pre-surgical planning and training, testing the effectiveness of different interventions, or developing new surgical procedures. The current direct additive manufacturing techniques cannot simultaneously ensure the flexibility and transparency of models required by some applications.
View Article and Find Full Text PDFMechanistic insights into transposon cleavage and integration by TnsB of ShCAST system.
Cell Rep
July 2023
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Chongqing Innovation Institute of China Pharmaceutical University, Chongqing 401135, China. Electronic address:
The type V-K CRISPR-associated transposons (CASTs) allow RNA-guided DNA integration and have great potential as a programmable site-specific gene insertion tool. Although all core components have been independently characterized structurally, the mechanism of how the transposase TnsB associates with AAA+ ATPase TnsC and catalyzes donor DNA cleavage and integration remains ambiguous. In this study, we demonstrate that TniQ-dCas9 fusion can direct site-specific transposition by TnsB/TnsC in ShCAST.
View Article and Find Full Text PDFTargeted DNA integration in human cells without double-strand breaks using CRISPR RNA-guided transposases.
bioRxiv
March 2023
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Traditional genome-editing reagents such as CRISPR-Cas9 achieve targeted DNA modification by introducing double-strand breaks (DSBs), thereby stimulating localized DNA repair by endogenous cellular repair factors. While highly effective at generating heterogenous knockout mutations, this approach suffers from undesirable byproducts and an inability to control product purity. Here we develop a system in human cells for programmable, DSB-free DNA integration using Type I CRISPR-associated transposons (CASTs).
View Article and Find Full Text PDFTargeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases.
Nat Biotechnol
January 2024
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Conventional genome engineering with CRISPR-Cas9 creates double-strand breaks (DSBs) that lead to undesirable byproducts and reduce product purity. Here we report an approach for programmable integration of large DNA sequences in human cells that avoids the generation of DSBs by using Type I-F CRISPR-associated transposases (CASTs). We optimized DNA targeting by the QCascade complex through protein design and developed potent transcriptional activators by exploiting the multi-valent recruitment of the AAA+ ATPase TnsC to genomic sites targeted by QCascade.
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