Results 1 to 10 of about 247,233 (219)

Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM

Nature Communications, 2022
The expansion of GGGGCC repeats in the C9ORF72 gene results in the production of disease causing abnormal proteins with polymeric glycine-arginine (poly-GR) and polymeric glycine-proline (poly-PR).
Anna B. Loveland, Egor Svidritskiy, Denis Susorov, Soojin Lee, Alexander Park, Sarah Zvornicanin, Gabriel Demo, Fen-Biao Gao, Andrei A. Korostelev   +8 more
doaj   +1 more source

PK-modifying anchors significantly alter clearance kinetics, tissue distribution, and efficacy of therapeutics siRNAs

Molecular Therapy: Nucleic Acids, 2022
Effective systemic delivery of small interfering RNAs (siRNAs) to tissues other than liver remains a challenge. siRNAs are small (∼15 kDa) and therefore rapidly cleared by the kidneys, resulting in limited blood residence times and tissue exposure ...
Bruno M.D.C. Godinho, Emily G. Knox, Samuel Hildebrand, James W. Gilbert, Dimas Echeverria, Zachary Kennedy, Reka A. Haraszti, Chantal M. Ferguson, Andrew H. Coles, Annabelle Biscans, Jillian Caiazzi, Julia F. Alterman, Matthew R. Hassler, Anastasia Khvorova   +13 more
doaj   +1 more source

Template-jumping prime editing enables large insertion and exon rewriting in vivo

Nature Communications, 2023
Targeted insertion of large DNA fragments holds promise for genome engineering and gene therapy. Prime editing (PE) effectively inserts short (400 bp) remains low and in vivo application has not been demonstrated.
Chunwei Zheng, Bin Liu, Xiaolong Dong, Nicholas Gaston, Erik J. Sontheimer, Wen Xue   +5 more
doaj   +1 more source

All-in-one adeno-associated virus delivery and genome editing by Neisseria meningitidis Cas9 in vivo

Genome Biology, 2018
Background Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy.
Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer   +5 more
doaj   +1 more source

CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling

Genome Medicine, 2019
CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in ...
Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue   +9 more
doaj   +1 more source

Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP

Nature Communications, 2021
EF-G drives ribosomal translocation along mRNA. Time-resolved cryo-EM captured translocation with EF-G•GTP—without inhibitors—revealing how EF-G uses ribosome fluctuations to drive translocation and GTP hydrolysis to leave at the right moment.
Christine E. Carbone, Anna B. Loveland, Howard B. Gamper, Ya-Ming Hou, Gabriel Demo, Andrei A. Korostelev   +5 more
doaj   +1 more source

2′-O-Methyl at 20-mer Guide Strand 3′ Termini May Negatively Affect Target Silencing Activity of Fully Chemically Modified siRNA

Molecular Therapy: Nucleic Acids, 2020
Small interfering RNAs (siRNAs) have the potential to treat a broad range of diseases. siRNAs need to be extensively chemically modified to improve their bioavailability, safety, and stability in vivo.
Sarah M. Davis, Jacquelyn Sousa, Lorenc Vangjeli, Matthew R. Hassler, Dimas Echeverria, Emily Knox, Anton A. Turanov, Julia F. Alterman, Anastasia Khvorova   +8 more
doaj   +1 more source

Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways

Genome Biology, 2021
Background Alternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression.
Carrie Kovalak, Scott Donovan, Alicia A. Bicknell, Mihir Metkar, Melissa J. Moore   +4 more
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Dendritic amphiphilic siRNA: Selective albumin binding, in vivo efficacy, and low toxicity

Molecular Therapy: Nucleic Acids, 2023
Although an increasing number of small interfering RNA (siRNA) therapies are reaching the market, the challenge of efficient extra-hepatic delivery continues to limit their full therapeutic potential. Drug delivery vehicles and hydrophobic conjugates are
Hassan H. Fakih, Qi Tang, Ashley Summers, Minwook Shin, Julianna E. Buchwald, Rosemary Gagnon, Vignesh N. Hariharan, Dimas Echeverria, David A. Cooper, Jonathan K. Watts, Anastasia Khvorova, Hanadi F. Sleiman   +11 more
doaj   +1 more source

The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing

Cell Reports, 2023
Summary: Argonaute/small RNA pathways and heterochromatin work together to propagate transgenerational gene silencing, but the mechanisms behind their interaction are not well understood.
Yue-He Ding, Humberto J. Ochoa, Takao Ishidate, Masaki Shirayama, Craig C. Mello   +4 more
doaj   +1 more source