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Marcello Maresca
AstraZeneca
17Publications
6H-index
143Citations
Publications 16
Newest
#1Alba Carreras (Sahlgrenska University Hospital)H-Index: 4
#2Luna Simona PaneH-Index: 2
Last.Marcello MarescaH-Index: 6
view all 20 authors...
Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target diseas...
1 CitationsSource
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#1Beeke Wienert (University of California, Berkeley)H-Index: 8
#2Stacia K. Wyman (University of California, Berkeley)H-Index: 4
Last.Jacob E. Corn (University of California, Berkeley)H-Index: 32
view all 14 authors...
CRISPR-Cas genome editing induces targeted DNA damage but can also affect off-target sites. Current off-target discovery methods work using purified DNA or specific cellular models but are incapable of direct detection in vivo. We developed DISCOVER-Seq (discovery of in situ Cas off-targets and verification by sequencing), a universally applicable approach for unbiased off-target identification that leverages the recruitment of DNA repair factors in cells and organisms. Tracking the precise recr...
13 CitationsSource
#1Matthew A. Coelho (AstraZeneca)H-Index: 1
#2Songyuan Li (AstraZeneca)H-Index: 1
Last.Benjamin J. M. Taylor (AstraZeneca)H-Index: 2
view all 9 authors...
Background Base Editing is a precise genome editing method that uses a deaminase-Cas9 fusion protein to mutate cytidine to thymidine in target DNA in situ without the generation of a double-strand break. However, the efficient enrichment of genetically modified cells using this technique is limited by the ability to detect such events.
2 CitationsSource
#1Cecilia Boreström (AstraZeneca)H-Index: 2
#2Anna Jonebring (AstraZeneca)H-Index: 6
Last.Anna Collén (AstraZeneca)H-Index: 3
view all 15 authors...
Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage ma...
16 CitationsSource
#1Salvatore Fabbiano (University of Geneva)H-Index: 6
#2Nicolas Suárez-Zamorano (University of Geneva)H-Index: 5
Last.Mirko Trajkovski (University of Geneva)H-Index: 12
view all 15 authors...
Summary Caloric restriction (CR) stimulates development of functional beige fat and extends healthy lifespan. Here we show that compositional and functional changes in the gut microbiota contribute to a number of CR-induced metabolic improvements and promote fat browning. Mechanistically, these effects are linked to a lower expression of the key bacterial enzymes necessary for the lipid A biosynthesis, a critical lipopolysaccharide (LPS) building component. The decreased LPS dictates the tone of...
15 CitationsSource
#1Amir Taheri-Ghahfarokhi (AstraZeneca)H-Index: 3
#2Benjamin J. M. Taylor (AstraZeneca)H-Index: 2
Last.Marcello Maresca (AstraZeneca)H-Index: 6
view all 12 authors...
12 CitationsSource
#1Pinar Akcakaya (AstraZeneca)H-Index: 3
#2Maggie L. Bobbin (Harvard University)H-Index: 4
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 22 authors...
CRISPR–Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1–6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe ‘verification of in vivo off-targets’ (VIVO), a highly sensitive strategy that can robustly identi...
48 CitationsSource
#1Jacqueline P. Robbins (University of Oxford)H-Index: 1
#2Leo W. Perfect ('KCL': King's College London)H-Index: 4
Last.Simon Lovestone (University of Oxford)H-Index: 83
view all 17 authors...
Our understanding of the molecular processes underlying Alzheimer’s disease (AD) is still limited, hindering the development of effective treatments and highlighting the need for human-specific models. Advances in identifying components of the amyloid cascade are progressing, including the role of the protein clusterin in mediating β-amyloid (Aβ) toxicity. Mutations in the clusterin gene (CLU), a major genetic AD risk factor, are known to have important roles in Aβ processing. Here we investigat...
4 CitationsSource
#1Shailesh Kumar Gupta (AstraZeneca)H-Index: 2
#2Agata Wesolowska-Andersen (Wellcome Trust Centre for Human Genetics)H-Index: 2
Last.Christian Honoré (Novo Nordisk)H-Index: 7
view all 20 authors...
Abstract Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-like cells and motor neurons. However, many of the current differentiation protocols lead to heterogeneous cell cultures containing cell types other than the targeted cell fate. Genetically modified human pluripotent stem cells reporting the expression of specific genes are of great value for differentiation protoco...
2 CitationsSource
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