siRNAmod: A database of experimentally validated chemically modified siRNAs

Dar, Showkat Ahmad; Thakur, Ashwani Kumar; Qureshi, Abid; Kumar, Manoj

doi:10.1038/srep20031

Cited by 62 publications

(45 citation statements)

References 57 publications

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“…Many different chemical configurations have been used to stabilize siRNAs, particularly combinations of 2′OMe, 2′F, and phosphorothioate 72, 79, 80 . Modifications that increase or decrease sugar flexibility have also been explored, including LNA and unlocked nucleic acid (UNA) 81 , but they are mainly used to introduce chemical asymmetry into duplex siRNAs.…”

Section: Chemical Evolution Of Sirnasmentioning

confidence: 99%

The chemical evolution of oligonucleotide therapies of clinical utility

2017

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After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency properties are derived primarily from the chemical structure of the oligonucleotide, while their target is defined by the base sequence. Thus, as oligonucleotides with a particular chemical design demonstrate appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue. To achieve clinical productivity, the chemical architecture of the oligonucleotide needs to be optimized as a whole, using a combination of sugar, backbone, nucleobase and 3′/5′-terminal modifications. A portfolio of chemistries can be used to confer drug like properties onto the oligonucleotide as a whole, with minor chemical changes often translating into major improvements in clinical efficacy. Outstanding challenges in oligonucleotide chemical development include optimization of chemical architectures to ensure long-term safety and to enable robust clinical activity beyond the liver.

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Section: Chemical Evolution Of Sirnasmentioning

confidence: 99%

The chemical evolution of oligonucleotide therapies of clinical utility

2017

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“…siRNA‐based therapeutic molecules for various diseases are under clinical evaluation. Recently, Dar et al . developed specialized databank for chemically modified siRNAs which contains a total of 4,894 chemically modified siRNA sequences.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of chemically modified siRNA: Recent trends

et al. 2017

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Small Interfering RNAs (siRNAs) are one of the valuable tools to investigate the functions of genes, and are also used for gene silencing. It has a wide scope in drug discovery through in vivo target validation. siRNA therapeutics are not optimal drug-like molecules due to poor bioavailability, immunogenic and off-target effects. In order to overcome the challenges associated with siRNA therapeutics, identification of appropriate chemical modifications that improves the stability, specificity and potency of siRNA is essential. This review focuses on the various chemical modifications and their implications in siRNA therapy.

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“…As a result, RNAis are being replaced by assays using more specific and tunable clustered regularly interspaced short palindromic repeat interference (CRISPRi) probes (Moore, ; Mandegar et al., ). The literature on the validation issues with RNA probes is relatively sparse compared to that documented for compounds and antibodies, and is probably a consequence of the limited database curation for chemically modified siRNAs (cm‐siRNAs; Dar, Thakur, Qureshi, & Kumar, )…”

Section: Rna Probe Validationmentioning

confidence: 99%

Reagent Validation to Facilitate Experimental Reproducibility

Williams

2018

CP Pharmacology

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Many results reported in the biomedical research literature cannot be independently reproduced, undermining the basic foundations of science. This overview is intended for researchers who are committed to improving the quality and integrity of biomedical science by raising awareness of both the sources of irreproducibility, and activities specifically targeted to address the issue. The irreproducibility of biomedical research is due to a variety of factors, known and unknown, that markedly influence experimental outcomes. Among the known factors are inadequate training or mentoring, or experimenter incompetence. These may result in flawed experimental design and execution that reflect a lack of planning, leading to an underpowering of a study, an absence of appropriate controls, selective data analysis, inappropriate statistical analysis, and/or investigator bias or fraud. Another frequently overlooked source of irreproducibility is failure to ensure that the equipment used is performing up to manufacturer specifications. Failure to validate/authenticate the experimental reagents is another source of irreproducibility. These include compounds, cell lines, antibodies, and the animal models used in a study. This overview discusses how a lack of validation of research reagents negatively impact experimental reproducibility, and provides guidelines to avoid these pitfalls. © 2018 by John Wiley & Sons, Inc.

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siRNAmod: A database of experimentally validated chemically modified siRNAs

Cited by 62 publications

References 57 publications

The chemical evolution of oligonucleotide therapies of clinical utility

The chemical evolution of oligonucleotide therapies of clinical utility

Therapeutic potential of chemically modified siRNA: Recent trends

Reagent Validation to Facilitate Experimental Reproducibility

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