10 Result(s)
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Cicera R. Lazzarotto
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Article
Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy
Spinal muscular atrophy (SMA) is caused by mutations in SMN1. SMN2 is a paralogous gene with a C•G-to-T•A transition in exon 7, which causes this exon to be skipped in most SMN2 transcripts, and results in low le...
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Article
Potent and uniform fetal hemoglobin induction via base editing
Inducing fetal hemoglobin (HbF) in red blood cells can alleviate β-thalassemia and sickle cell disease. We compared five strategies in CD34+ hematopoietic stem and progenitor cells, using either Cas9 nuclease or ...
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Article
In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice
Transplantation of B cells engineered ex vivo to secrete broadly neutralizing antibodies (bNAbs) has shown efficacy in disease models. However, clinical translation of this approach would require specialized m...
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Article
Defining genome-wide CRISPR–Cas genome-editing nuclease activity with GUIDE-seq
Genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) is a sensitive, unbiased, genome-wide method for defining the activity of genome-editing nucleases in living cell...
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Article
Base editing of haematopoietic stem cells rescues sickle cell disease in mice
Sickle cell disease (SCD) is caused by a mutation in the β-globin gene HBB1. We used a custom adenine base editor (ABE8e-NRCH)2,3 to convert the SCD allele (HBBS) into Makassar β-globin (HBBG), a non-pathogenic v...
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Article
Open AccessPrime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression
Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (...
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Article
CHANGE-seq reveals genetic and epigenetic effects on CRISPR–Cas9 genome-wide activity
Current methods can illuminate the genome-wide activity of CRISPR–Cas9 nucleases, but are not easily scalable to the throughput needed to fully understand the principles that govern Cas9 specificity. Here we d...
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Article
Open AccessEfficient correction of a deleterious point mutation in primary horse fibroblasts with CRISPR-Cas9
Phenotypic selection during animal domestication has resulted in unwanted incorporation of deleterious mutations. In horses, the autosomal recessive condition known as Glycogen Branching Enzyme Deficiency (GBE...
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Article
Highly efficient therapeutic gene editing of human hematopoietic stem cells
Re-expression of the paralogous γ-globin genes (HBG1/2) could be a universal strategy to ameliorate the severe β-globin disorders sickle cell disease (SCD) and β-thalassemia by induction of fetal hemoglobin (HbF,...
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Article
Defining CRISPR–Cas9 genome-wide nuclease activities with CIRCLE-seq
Circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) is a sensitive and unbiased method for defining the genome-wide activity (on-target and off-target) of CRISPR–Cas9 nuclease...
