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Articles by Marcello Maresca
Unveiling the cut-and-repair cycle of designer nucleases in human stem and T cells via CLEAR-time dPCR - Nature Communications
Abstract DNA repair mechanisms in human primary cells, including error-free repair, and, recurrent nuclease cleavage events, remain largely uncharacterised. We elucidate gene-editing related repair processes using Cleavage and Lesion Evaluation via Absolute Real-time dPCR (CLEAR-time dPCR), an ensemble of multiplexed dPCR assays that quantifies genome integrity at targeted sites.
Dual inhibition of DNA-PK and Polϴ boosts precision of diverse prime editing systems - Nature Communications
Abstract Prime editing is a genome engineering tool that allows installation of various small edits with high precision. However, prime editing efficiency and purity can vary widely across different edits, genomic targets, and cell types. Prime editing typically offers more precise editing outcomes compared to other genome editing methods such as homology-directed repair. However, it can still result in significant rates of unintended editing outcomes, such as indels or imprecise prime edits.
Modified pegRNAs mitigate scaffold-derived prime editing by-products - Nature Communications
Abstract Prime editors (PEs) employ reverse transcriptase (RT) to install genomic edits using a template within the prime editing guide RNA (pegRNA). RT creates a 3’ genomic flap containing the intended edit. However, reverse transcription can continue beyond the template, incorporating the pegRNA scaffold sequence into the 3’ flap. These scaffold-derived by-products can be installed alongside the intended edit, reducing prime editing precision.
Prime Editing: Mechanistic Insights and DNA Repair Modulation
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Optimized prime editing of the Alzheimer’s disease-associated APOE4 mutation
ReportVolume 20, Issue 1102372Open access Affiliations & Notes 1Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden 2Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Cambridge, UK Article Info Publication History: Received October 1, 2024; Revised November 5, 2024; Accepted November 6, 2024; Published online December 5, 2024 DOI: 10.1016/j.stemcr.2024.11.002 External LinkAlso available on...
Optimized prime editing of the Alzheimer’s disease-associated APOE4 mutation
ReportOnline nowOpen access 1Genome Engineering, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Gothenburg, Sweden 2Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D Unit, AstraZeneca, Cambridge, UK Publication History: Received October 1, 2024; Revised November 5, 2024; Accepted November 6, 2024; Published online December 5, 2024 DOI: 10.1016/j.stemcr.2024.11.002Also available on ScienceDirect Copyright: © 2024 The Author(s).
Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles - Nature Communications
Abstract Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues.
TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis - Nature Communications
Abstract The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition.
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