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View article: Blocking somatic repeat expansion and lowering huntingtin via RNA interference synergize to prevent Huntington’s disease pathogenesis in mice
Blocking somatic repeat expansion and lowering huntingtin via RNA interference synergize to prevent Huntington’s disease pathogenesis in mice Open
Huntington’s disease (HD) is a progressive neurodegenerative disorder with no approved therapies. Two major molecular drivers—somatic expansion of inherited CAG repeats and toxic mutant HTT (mHTT) variants—lead to neuronal dysfunction. Des…
View article: Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy
Systematic analysis of siRNA and mRNA features impacting fully chemically modified siRNA efficacy Open
Chemically modified small interfering RNAs (siRNAs) are a promising drug class that silences disease-causing genes via mRNA degradation. Both siRNA-specific features (e.g. sequence, modification pattern, and structure) and target mRNA-spec…
View article: Lowering the <i>HTT1a</i> transcript as an effective therapy for Huntington’s disease
Lowering the <i>HTT1a</i> transcript as an effective therapy for Huntington’s disease Open
Lowering the levels of HTT transcripts has been a major focus of therapeutic development for Huntington’s disease (HD), but which transcript should be lowered? HD is caused by a CAG repeat expansion in exon 1 of the HTT gene, and the rate …
View article: Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model
Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model Open
MECP2 duplication syndrome (MDS) is a rare X-linked neurodevelopmental disorder caused by duplications of the dosage-sensitive methyl-CpG-binding protein 2 (MECP2) gene. Developing effective therapies for MDS is particularly challenging du…
View article: Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model
Single-dose administration of therapeutic divalent siRNA targeting MECP2 prevents lethality for one year in an MECP2 duplication mouse model Open
MECP2 duplication syndrome (MDS) is a rare X-linked neurodevelopmental disorder caused by duplications of the dosage-sensitive methyl-CpG-binding protein 2 (MECP2) gene. Developing effective therapies for MDS is particularly challenging du…
View article: Mutant huntingtin exon 1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MutS Homolog 3 silencing and aggregation
Mutant huntingtin exon 1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MutS Homolog 3 silencing and aggregation Open
HTT1a was identified in human and mouse Huntington’s disease brain as the pathogenic exon 1 mRNA generated from aberrant splicing between exon 1 and 2 of HTT that contributes to aggregate formation and neuronal dysfunction. Detection of th…
View article: Mutant Huntingtin exon1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MSH3 silencing, and aggregation
Mutant Huntingtin exon1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MSH3 silencing, and aggregation Open
HTT1a was identified in human and mouse Huntington’s disease brain as the pathogenic exon 1 mRNA generated from aberrant splicing between exon 1 and 2 of HTT that contributes to aggregate formation and neuronal dysfunction. 1 Detection of …
View article: Suppression of Huntington’s Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding
Suppression of Huntington’s Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding Open
Huntington’s disease (HD) arises from a CAG expansion in the huntingtin ( HTT ) gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant HTT mRNA (m HTT ) and protein (mHTT) with t…
View article: Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023
Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023 Open
Importance Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on …
View article: mRNA Nuclear Clustering Leads to a Difference in Mutant Huntingtin mRNA and Protein Silencing by siRNAs <i>In Vivo</i>
mRNA Nuclear Clustering Leads to a Difference in Mutant Huntingtin mRNA and Protein Silencing by siRNAs <i>In Vivo</i> Open
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the first exon of the huntingtin gene (HTT). Oligonucleotide therapeutics, such as short interfering RNA (siRNA), reduce …
View article: mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs<i>in vivo</i>
mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs<i>in vivo</i> Open
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the first exon of the huntingtin gene ( HTT ). Oligonucleotide therapeutics, such as short interfering RNA (siRNA), reduce level…
View article: Challenges of Assessing Exon 53 Skipping of the Human <i>DMD</i> Transcript with Locked Nucleic Acid-Modified Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy
Challenges of Assessing Exon 53 Skipping of the Human <i>DMD</i> Transcript with Locked Nucleic Acid-Modified Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy Open
Antisense oligonucleotide (AON)-mediated exon skipping is a promising therapeutic approach for Duchenne muscular dystrophy (DMD) patients to restore dystrophin expression by reframing the disrupted open reading frame of the DMD tran…
View article: Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease
Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease Open
(Molecular Therapy 31, 1661–1674; June 2023) In the originally published version of this article, the data for MSH2, PMS1, and PMS2 in Figure 6 were unintentionally duplicated. After reviewing the original data, the authors found that the …
View article: Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease
Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease Open
Huntington's disease (HD) is a severe neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat tract in the huntingtin gene. Inheritance of expanded CAG repeats is needed for HD manifestation, but further somatic …
View article: Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection
Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection Open
The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are …
View article: Di-valent siRNA Mediated Silencing of MSH3 Blocks Somatic Repeat Expansion in Mouse Models of Huntington’s Disease
Di-valent siRNA Mediated Silencing of MSH3 Blocks Somatic Repeat Expansion in Mouse Models of Huntington’s Disease Open
Huntington’s Disease (HD) is a severe neurodegenerative disorder caused by expansion of the CAG trinucleotide repeat tract in the huntingtin gene. Inheritance of expanded CAG repeats is needed for HD manifestation, but further somatic expa…
View article: CCDC 2151865: Experimental Crystal Structure Determination
CCDC 2151865: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles
Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles Open
View article: The Role of Patient Involvement When Developing Therapies
The Role of Patient Involvement When Developing Therapies Open
The drug development process is a long and arduous one, especially for rare diseases. Patient and patient representatives can and should be involved in this process from an early stage, since they have the perspective of living with a dise…
View article: Small nucleic acids and the path to the clinic for anti-CRISPR
Small nucleic acids and the path to the clinic for anti-CRISPR Open
View article: CCDC 1576722: Experimental Crystal Structure Determination
CCDC 1576722: Experimental Crystal Structure Determination Open
View article: CCDC 1576721: Experimental Crystal Structure Determination
CCDC 1576721: Experimental Crystal Structure Determination Open
View article: Mechanochemical Synthesis of Short DNA Fragments
Mechanochemical Synthesis of Short DNA Fragments Open
We report the general and rapid synthesis of short DNA fragments of controllable sequence and length using multi-step, one-pot mechanochemical reactions, without bulk solvent or the need to isolate intermediates. We demonstrate, for the fi…
View article: Mechanochemical Synthesis of Short DNA Fragments
Mechanochemical Synthesis of Short DNA Fragments Open
We report the general and rapid synthesis of short DNA fragments of controllable sequence and length using multi-step, one-pot mechanochemical reactions, without bulk solvent or the need to isolate intermediates. We demonstrate, for the fi…
View article: Mechanochemical Synthesis of Short DNA Fragments
Mechanochemical Synthesis of Short DNA Fragments Open
We report the general and rapid synthesis of short DNA fragments of controllable sequence and length using multi-step, one-pot mechanochemical reactions, without bulk solvent or the need to isolate intermediates. We demonstrate, for the fi…
View article: Improving oligonucleotide as therapeutics: from design, synthesis, and conformational analysis to gene silencing and gene editing applications
Improving oligonucleotide as therapeutics: from design, synthesis, and conformational analysis to gene silencing and gene editing applications Open
View article: Rationally Designed Anti-CRISPR Nucleic Acid Inhibitors of CRISPR-Cas9
Rationally Designed Anti-CRISPR Nucleic Acid Inhibitors of CRISPR-Cas9 Open
Clustered regularly interspaced short palindromic repeat (CRISPR) RNAs and their associated effector (Cas) enzymes are being developed into promising therapeutics to treat disease. However, CRISPR-Cas enzymes might produce unwanted gene ed…
View article: Extensive CRISPR RNA modification reveals chemical compatibility and structure-activity relationships for Cas9 biochemical activity
Extensive CRISPR RNA modification reveals chemical compatibility and structure-activity relationships for Cas9 biochemical activity Open
CRISPR (clustered regularly interspaced short palindromic repeat) endonucleases are at the forefront of biotechnology, synthetic biology and gene editing. Methods for controlling enzyme properties promise to improve existing applications a…
View article: Activating frataxin expression by single-stranded siRNAs targeting the GAA repeat expansion
Activating frataxin expression by single-stranded siRNAs targeting the GAA repeat expansion Open
View article: Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat
Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat Open
Friedreich's Ataxia (FA) is an inherited neurologic disorder caused by an expanded GAA repeat within intron 1 of the frataxin (FXN) gene that reduces expression of FXN protein. Agents that increase expression of FXN have the potential to a…