Chronic lymphocytic leukemia (CLL) is a high incidence B cell leukemia with a highly variable clinical course, leading to survival times ranging from months to several decades. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression levels of genes by binding to the untranslated regions of transcripts. Although miRNAs have been previously shown to play a crucial role in CLL development, progression and treatment resistance, their further processing and diversification by RNA editing (specifically adenosine to inosine or cytosine to uracil deamination) has not been addressed so far. In this study, we analyzed next generation sequencing data to provide a detailed map of adenosine to inosine and cytosine to uracil changes in miRNAs from CLL and normal B cells. Our results reveal that in addition to a CLL-specific expression pattern, there is also specific RNA editing of many miRNAs, particularly miR-3157 and miR-6503, in CLL. Our data draw further light on how miRNAs and miRNA editing might be implicated in the pathogenesis of the disease.
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http://dx.doi.org/10.3390/cancers12051159 | DOI Listing |
Curr Cardiol Rep
January 2025
The Pauley Heart Center, Virginia Commonwealth University, 1200 East Broad Street West Hospital, 8th Floor, West Wing, Richmond, VA, 23231, USA.
Purpose Of Review: In this article, we describe current and newer TTR stabilizers, TTR silencers which include small interfering RNA agents (siRNA), antisense oligonucleotides (ASO) and CRISPR-Cas9 gene editing, and TTR depleters, which investigates the use of monoclonal antibodies to remove amyloid fibril deposits for patients with advanced disease.
Recent Findings: Once thought to be a rare and fatal condition, increased recognition, improved non-invasive diagnostic tools, and the explosive development of novel therapies, has transformed the landscape of transthyretin amyloid cardiomyopathy (ATTR-CM). Advances in cardiac imaging with respect to echocardiography, cardiac magnetic resonance imaging (CMR), and radionuclide bone scintigraphy has increased the diagnosis of ATTR-CM over the last twenty years.
Anal Chem
January 2025
Analytical Chemistry Group, ‡VI-NEXT Group, Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591-6706, United States.
Phosphorothioate (PS) modifications in single-guided RNA (sgRNA) are crucial for genome editing applications using the CRISPR/Cas9 system. These modifications may enhance sgRNA stability, pharmacokinetics, and binding to targets, thereby facilitating the desired genetic alterations. Incorporating multiple PS groups at varying positions may introduce chiral centers into the sgRNA backbone, resulting in a complex mixture of constitutional- and stereoisomers that challenges current analytical capabilities for reliable identification and quantification.
View Article and Find Full Text PDFJ Control Release
January 2025
Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland. Electronic address:
Gene editing technologies, particularly clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, have revolutionized the ability to modify gene sequences in living cells for therapeutic purposes. Delivery of CRISPR/Cas ribonucleoprotein (RNP) is preferred over its DNA and RNA formats in terms of gene editing effectiveness and low risk of off-target events. However, the intracellular delivery of RNP poses significant challenges and necessitates the development of non-viral vectors.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112.
Cell Mol Life Sci
January 2025
Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Dynamic changes in DNA methylation are prevalent during the progression of breast cancer. However, critical alterations in aberrant methylation and gene expression patterns have not been thoroughly characterized. Here, we utilized guide positioning sequencing (GPS) to conduct whole-genome DNA methylation analysis in a unique human breast cancer progression model: MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and metastatic carcinoma).
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