Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for a...
The CRISPR/Cas9 system (clustered regularly interspaced short palindromic repeat-associated protein 9) is a powerful genome-editing tool in animals, plants, and humans. This system has some advantages, such as a high on-target mutation rate (targetin...
The CRISPR/nCas9-based cytosine base editors (CBEs) and adenine base editors (ABEs) are capable of catalyzing C•G to T•A or A•T to G•C conversions, respectively, and have become new, powerful tools for achieving precise genetic ch...
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 endonuclease (Cas9) derived from bacterial adaptive immune systems is a revolutionary tool used in both basic and applied science. It is a versatile system tha...
CRISPR/Cas9 is a popular genome editing technology, yet its clinical application is hindered by off-target effects. Many deep learning-based methods are available for off-target prediction. However, few can predict off-target activities with insertio...
In RNA interference (RNAi), small interfering RNA (siRNA) suppresses the expression of its target mRNA with a perfect complementary sequence. In addition, siRNA also suppresses the expression of unintended mRNAs with partially complementary sequences...
The CRISPR-Cas system has evolved into a cutting-edge technology that has transformed the field of biological sciences through precise genetic manipulation. CRISPR/Cas9 nuclease is evolving into a revolutionizing method to edit any gene of any specie...
Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a novel class of glucose-lowering drugs, have revolutionized the management of heart failure with reduced and preserved ejection fraction, regardless of the presence of diabetes, and are curre...
The molecular revolution could lead drug discovery from chance observation to the rational design of new classes of drugs that could simultaneously be more effective and less toxic. Unfortunately, we are witnessing some failure in this sense, and the...
Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest th...
Specific genetic variants in the mitochondrially encoded 12S ribosomal RNA gene (MT-RNR1) cause aminoglycoside-induced irreversible hearing loss. Mitochondrial DNA is usually not included in targeted sequencing experiments; however, off-target data m...
Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function t...
Background/Objectives: Peptide amphiphile micelles (PAMs) are an exciting nanotechnology currently being studied for a variety of biomedical applications, especially for drug delivery. Specifically, PAMs can enhance in vivo trafficking, cell-targetin...
Chemical modifications are the standard for small interfering RNAs (siRNAs) in therapeutic applications, but predicting their off-target effects remains a significant challenge. Current approaches often rely on sequence-based encodings, which fail to...
Background: The CRISPR-Cas9 system has emerged as one of the most promising gene-editing technologies in biology. However, off-target effects remain a significant challenge. While recent advances in deep learning have led to the development of models...
CRISPR-Cas9 has emerged as a remarkably powerful gene editing tool and has advanced both research and gene therapy applications. Machine learning models have been developed to predict off-target cleavages. Despite progress, accuracy, stability, and i...
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)—associated protein 9 (Cas9) system is a groundbreaking gene-editing tool, which has been widely adopted in biomedical research. However, the guide RNAs in CRISPR-Cas9 system...
Clostridium butyricum Argonaute (CbAgo) can achieve DNA-guided DNA recognition and cleavage at physiological temperatures (~37 °C), making it a promising tool for gene editing. However, its significant off-target effects, particularly associated...
The process of discovering small molecule drugs involves screening numerous compounds and optimizing the most promising ones, both in vitro and in vivo. However, approximately 90% of these optimized candidates fail during trials due to unexpected tox...
Endogenous siRNAs (endo-siRNAs) are key regulators of RNA silencing in plants and worms; however, the biogenesis and function of endogenous siRNAs in mammals remain largely unknown. We previously demonstrated that human telomerase reverse transcripta...
Developing a therapeutic antibody is a long, tedious, and expensive process. Many obstacles need to be overcome, such as biophysical properties (issues of solubility, stability, weak production yields, etc.), as well as cross-reactivity and subsequen...
MicroRNA (miRNA) transfection is known to degrade target mRNAs and to decrease mRNA expression. In contrast to the notion that most of the gene expression alterations caused by miRNA transfection involve downregulation, they often involve both up- an...
Base-editing technologies, particularly cytosine base editors (CBEs), allow precise gene modification without introducing double-strand breaks; however, unintended RNA off-target effects remain a critical concern and are under studied. To address thi...
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-mediated genome editing holds remarkable promise for the treatment of human genetic diseases. However, the possibility of off-target Cas9 activity rem...
The increasing life expectancy of humans has led to an increase in the number of patients with chronic diseases and organ failure. However, the imbalance between the supply and the demand for human organs is a serious problem in modern transplantolog...
Background: Genome editing at specific loci is an innovative therapeutic approach; however, it faces many challenges, so optimizing delivery vectors is essential to enhance the safety and efficacy of the CRISPR/Cas9 system. This study investigated wh...
Accurate detection of biomolecular interactions is essential in many areas, from the detection of the presence of biomarkers in the clinic to the development of therapeutic drugs and biologics in biopharma to the understanding of various biological p...
Orchard pesticide off-target deposition and drift cause substantial soil and water pollution, and other environmental pollution. Orchard target-oriented spraying technologies have been used to reduce the deposition and drift caused by off-target spra...
Chemical probes are of central relevance for chemical biology. To unambiguously explore the role of target proteins in triggering or mediating biological functions, small molecules used as probes should ideally be target-specific; at least, they shou...
To improve the deposition rate of thin films, a novel oscillating pulse magnetron sputtering technology (OPMS) was developed to substitute the traditional high-power impulse magnetron sputtering (HiPIMS). Meanwhile, the relative density and the mecha...
The Cre-LoxP conditional knockout strategy has been used extensively to study gene function in a specific cell-type. In this study, the authors tried to engineer mice in which the Dbc1 gene is conditionally knocked out in Treg cells. Unexpectedly, th...
Leishmaniasis is a vector-borne disease of global concern, transmitted by sand flies of the genera Lutzomyia and Phlebotomus. Attractive toxic sugar baits (ATSBs) have emerged as a promising alternative for vector control, leveraging the sugar-feedin...
The high sequence specificity of minor groove-binding N-methylpyrrole-N-methylimidazole polyamides have made significant advances in cancer and disease biology, yet there have been few comprehensive reports on their off-target effects, most likely as...
The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in maintaining various physiological processes in the body, including blood pressure regulation, electrolyte balance, and overall cardiovascular health. However, any com...
Throughout the human lifespan, from conception to the end of life, small molecules have an intrinsic relationship with numerous physiological processes. The investigation into small-molecule targets holds significant implications for pharmacological...
CRISPR/Cas9 technology is capable of precisely editing genomes and is at the heart of various scientific and medical advances in recent times. The advances in biomedical research are hindered because of the inadvertent burden on the genome when genom...
Gene editing that makes target gene modification in the genome by deletion or addition has revolutionized the era of biomedicine. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 emerged as a substantial tool due to its simplic...
Background/Objectives: CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats)-associated protein 9 is now widely used in agriculture and medicine. Off-target effects can lead to unexpected results that may be harmful, and these effec...
CRISPR/Cas9 is a powerful genome-editing technology that has been widely applied in targeted gene repair and gene expression regulation. One of the main challenges for the CRISPR/Cas9 system is the occurrence of unexpected cleavage at some sites (off...
Weeds can cause significant yield losses and will continue to be a problem for agricultural production due to climate change. Dicamba is widely used to control weeds in monocot crops, especially genetically engineered dicamba-tolerant (DT) dicot crop...
The reprogrammable CRISPR/Cas9 genome editing tool’s growing popularity is hindered by unwanted off-target effects. Efforts have been directed toward designing efficient guide RNAs as well as identifying potential off-target threats, yet factor...
CRISPR/Cas9 genome editing holds promise for precise genetic modifications, yet off-target effects remain a concern—particularly in gene families with high sequence similarity. In this study, we present a computational framework for analyzing e...
The lymphocyte-specific protein tyrosine kinase (LCK) is a critical target in leukemia treatment. However, potential off-target interactions involving LCK can lead to unintended consequences. This underscores the importance of accurately predicting t...
Small interfering RNA (siRNA) has been recognized as a powerful gene-silencing tool. For therapeutic application, chemical modification is often required to improve the properties of siRNA, including its nuclease resistance, activity, off-target effe...
CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated protein) nucleases enable precise genome editing, but off-target cleavage remains a critical challenge. Here, we report the development of MAD7_HF, a high-fidel...
Deciphering the protein posttranslational modification (PTM) code is one of the greatest biochemical challenges of our time. Phosphorylation and ubiquitylation are key PTMs that dictate protein function, recognition, sub-cellular localization, stabil...
The potential of targeting the Renin-Angiotensin-Aldosterone System (RAAS) as a treatment for the coronavirus disease 2019 (COVID-19) is currently under investigation. One way to combat this disease involves the repurposing of angiotensin receptor bl...
We characterized the in vitro safety and bioavailability profile of silvestrol, a compound effective against various viruses, such as corona- and Ebolaviruses, with an EC50 value of about 5 nM. The cytotoxic profile of silvestrol was assessed in vari...
T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-ta...
Background/Objectives: Drug-Induced Kidney Injury (DIKI) presents a significant challenge in drug development, often leading to clinical-stage failures. The early prediction of DIKI risk can improve drug safety and development efficiency. Existing mo...
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