-
Article
Open AccessGalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy
Lipid nanoparticles have demonstrated utility in hepatic delivery of a range of therapeutic modalities and typically deliver their cargo via low-density lipoprotein receptor-mediated endocytosis. For patients ...
-
Article
Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a common childhood cancer that shares features with develo** skeletal muscle. Yet, the conservation of cellular hierarchy with human muscle development and the identification of mol...
-
Article
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates
Gene-editing technologies, which include the CRISPR–Cas nucleases1–3 and CRISPR base editors4,5, have the potential to permanently modify disease-causing genes in patients6. The demonstration of durable editing i...
-
Article
CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells
CRISPR-guided DNA cytosine and adenine base editors are widely used for many applications1–4 but primarily create DNA base transitions (that is, pyrimidine-to-pyrimidine or purine-to-purine). Here we describe the...
-
Article
A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing
Existing adenine and cytosine base editors induce only a single type of modification, limiting the range of DNA alterations that can be created. Here we describe a CRISPR–Cas9-based synchronous programmable ad...
-
Article
Open AccessTwo faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already diffe...
-
Article
Open AccessAssessment of computational methods for the analysis of single-cell ATAC-seq data
Recent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysi...
-
Article
Open AccessHigh levels of AAV vector integration into CRISPR-induced DNA breaks
Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In ...
-
Article
CRISPR DNA base editors with reduced RNA off-target and self-editing activities
Cytosine or adenine base editors (CBEs or ABEs) can introduce specific DNA C-to-T or A-to-G alterations1–4. However, we recently demonstrated that they can also induce transcriptome-wide guide-RNA-independent edi...
-
Article
Allele-specific gene editing prevents deafness in a model of dominant progressive hearing loss
Since most dominant human mutations are single nucleotide substitutions1,2, we explored gene editing strategies to disrupt dominant mutations efficiently and selectively without affecting wild-type alleles. Howev...
-
Article
Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors
CRISPR–Cas base-editor technology enables targeted nucleotide alterations, and is being increasingly used for research and potential therapeutic applications1,2. The most widely used cytosine base editors (CBEs) ...
-
Article
Open AccessMolecularly distinct models of zebrafish Myc-induced B cell leukemia
-
Article
In vivo CRISPR editing with no detectable genome-wide off-target mutations
CRISPR–Cas genome-editing nucleases hold substantial promise for develo** human therapeutic applications1–6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated...
-
Article
Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia
-
Article
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requir...
-
Chapter and Conference Paper
Analysis of Word Symmetries in Human Genomes Using Next-Generation Sequencing Data
We investigate Chargaff’s second parity rule and its extensions in the human genome, and evaluate its statistical significance. This phenomenon has been previously investigated in the reference human genome, b...
-
Chapter and Conference Paper
Segmentation of DNA into Coding and Noncoding Regions Based on Inter-STOP Symbols Distances
In this study we set to explore the potentialities of the inter-genomic symbols distance for finding the coding regions in DNA sequences. We use the distance between STOP symbols in the DNA sequence and a chi-...
-
Protocol
Compressing Resequencing Data with GReEn
Genome sequencing centers are flooding the scientific community with data. A single sequencing machine can nowadays generate more data in one day than any existing machine could have produced throughout the en...
-
Chapter and Conference Paper
Exon: A Web-Based Software Toolkit for DNA Sequence Analysis
Recent advances in DNA sequencing methodologies have caused an exponential growth of publicly available genomic sequence data. By consequence, many computational biologists have intensified studies in order to...
-
Chapter and Conference Paper
Distances between Dinucleotides in the Human Genome
We developed a methodology to process DNA sequences based on the inter-dinucleotide distances and we characterized the inter-dinucleotide distance distributions of the human genome. The distance distribution o...
