scholarly journals Medicinal Applications of Antisense Oligonucleotides: A Review

2020 ◽  
Vol 5 (02) ◽  
pp. 30-36
Author(s):  
Kavya Pandiri ◽  
Mohammed Abdul Samad ◽  
Nadeem Abbas Gulamus ◽  
Hajera Khanam
Keyword(s):  
High Throughput ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Therapeutic Approach ◽  
Antisense Technology ◽  
Dna And Rna ◽  
Wide Range ◽  
High Throughput Method ◽  
Delivery Strategies ◽  
Antisense Oligonucleotide Therapy

Antisense technology has emerged as a fast and conceivably high-throughput method for repressing genes due to advancement in knowledge about DNA and RNA physiology. The limitations of antisense oligonucleotide therapy in delivery strategies have been overcome in recent years. Antisense oligonucleotide treatment was effectively applied towards targeting a wide range of therapeutic areas. With ongoing approvals of antisense oligonucleotides, there is an expanding enthusiasm for increasing the utilization of these compounds for curing various infections. This short survey gives a far-reaching comprehension of applications of antisense technology, how they can be utilized therapeutically, and current endeavors to grow new antisense oligonucleotide treatments that will add a forthcoming therapeutic approach for the treatment of various diseases.

scholarly journals Antisense Oligonucleotides: Pharmacology and Delivery Strategies

2020 ◽  
Vol 5 (01) ◽  
pp. 7-11
Author(s):  
Mohammed Abdul Samad ◽  
Kavya Pandiri ◽  
Anjani Prasad Bojanapally
Keyword(s):  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Delivery Methods ◽  
Fundamental Idea ◽  
Therapeutic Outcomes ◽  
Wide Range ◽  
Effective Delivery ◽  
Delivery Strategies ◽  
Antisense Oligonucleotide Therapy ◽  
Modify Protein

Antisense oligonucleotide therapy is a dominant drug discovery approach that can explicitly modify protein synthesis through numerous mechanisms. The limitations of antisense oligonucleotide (ASO) therapy in delivery strategies have been overcome in recent years with different ligands carriers, as well as, through nanocarriers. ASO therapy was successfully applied towards targeting a wide range of therapeutic areas. There is an expanding enthusiasm in extending the utilization of antisense compounds to numerous different diseases due to their safe and potential therapeutic outcomes. Thus, the present review attempted to elaborate on the fundamental idea of antisense technology, approaches, and safe and effective delivery methods.

scholarly journals Wrangling RNA: Antisense oligonucleotides for neurological disorders

2019 ◽  
Vol 11 (511) ◽  
pp. eaay2069 ◽  
Author(s):  
Kevin Talbot ◽  
Matthew J. A. Wood
Keyword(s):  
Spinal Muscular Atrophy ◽  
Effective Treatment ◽  
Neurological Disorders ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Muscular Atrophy ◽  
Antisense Oligonucleotide Therapy

Effective treatment of spinal muscular atrophy with antisense oligonucleotide therapy opens the door to treating other neurological disorders with this approach.

scholarly journals seqCAT: a Bioconductor R-package for variant analysis of high throughput sequencing data

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1466 ◽  
Author(s):  
Erik Fasterius ◽  
Cristina Al-Khalili Szigyarto
Keyword(s):  
Genetic Variation ◽  
Liver Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
R Package ◽  
Ease Of Use ◽  
Sequencing Data ◽  
Dna And Rna ◽  
High Throughput Sequencing Data ◽  
Wide Range

High throughput sequencing technologies are flourishing in the biological sciences, enabling unprecedented insights into e.g. genetic variation, but require extensive bioinformatic expertise for the analysis. There is thus a need for simple yet effective software that can analyse both existing and novel data, providing interpretable biological results with little bioinformatic prowess. We present seqCAT, a Bioconductor toolkit for analysing genetic variation in high throughput sequencing data. It is a highly accessible, easy-to-use and well-documented R-package that enables a wide range of researchers to analyse their own and publicly available data, providing biologically relevant conclusions and publication-ready figures. SeqCAT can provide information regarding genetic similarities between an arbitrary number of samples, validate specific variants as well as define functionally similar variant groups for further downstream analyses. Its ease of use, installation, complete data-to-conclusions functionality and the inherent flexibility of the R programming language make seqCAT a powerful tool for variant analyses compared to already existing solutions. A publicly available dataset of liver cancer-derived organoids is analysed herein using the seqCAT package, demonstrating that the organoids are genetically stable. A previously known liver cancer-related mutation is additionally shown to be present in a sample though it was not listed in the original publication. Differences between DNA- and RNA-based variant calls in this dataset are also analysed revealing a high median concordance of 97.5%.

scholarly journals Antisense oligonucleotide therapy for KCNT1 encephalopathy

2020 ◽  
Author(s):  
Lisseth Estefania Burbano ◽  
Melody Li ◽  
Nikola Jancovski ◽  
Paymaan Jafar-Nejad ◽  
Kay Richards ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Antisense Oligonucleotide ◽  
Therapeutic Approach ◽  
Bolus Injection ◽  
De Novo ◽  
Proof Of Concept ◽  
Epileptic Encephalopathies ◽  
Behavioral Abnormalities ◽  
Promising Therapeutic Approach ◽  
Antisense Oligonucleotide Therapy

ABSTRACTDevelopmental and epileptic encephalopathies (DEE) are characterized by pharmacoresistant seizures with concomitant intellectual disability. Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe of these syndromes. De novo mutations in ion channels, including gain-of-function variants in KCNT1, have been found to play a major role in the etiology of EIMFS. Here, we test a potential precision therapeutic approach in KCNT1-associated DEE using a gene silencing antisense oligonucleotide (ASO) approach. The homozygous p.P924L (L/L) mouse model recapitulates the frequent, debilitating seizures and developmental compromise that are seen in patients. After a single intracerebroventricular bolus injection of a Kcnt1 gapmer ASO in symptomatic mice at postnatal day 40, seizure frequency was significantly reduced, behavioral abnormalities improved, and overall survival was extended compared to mice treated with a control ASO (non-hybridizing sequence). ASO administration at neonatal age was also well-tolerated and effective in controlling seizures and extending the lifespan of treated animals. The data presented here provides a proof of concept for ASO-based gene silencing as a promising therapeutic approach in KCNT1-associated epilepsies.

scholarly journals seqCAT: a Bioconductor R-package for variant analysis of high throughput sequencing data

F1000Research ◽  
2019 ◽  
Vol 7 ◽  
pp. 1466 ◽  
Author(s):  
Erik Fasterius ◽  
Cristina Al-Khalili Szigyarto
Keyword(s):  
Genetic Variation ◽  
Liver Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
R Package ◽  
Ease Of Use ◽  
Sequencing Data ◽  
Dna And Rna ◽  
High Throughput Sequencing Data ◽  
Wide Range

High throughput sequencing technologies are flourishing in the biological sciences, enabling unprecedented insights into e.g. genetic variation, but require extensive bioinformatic expertise for the analysis. There is thus a need for simple yet effective software that can analyse both existing and novel data, providing interpretable biological results with little bioinformatic prowess. We present seqCAT, a Bioconductor toolkit for analysing genetic variation in high throughput sequencing data. It is a highly accessible, easy-to-use and well-documented R-package that enables a wide range of researchers to analyse their own and publicly available data, providing biologically relevant conclusions and publication-ready figures. SeqCAT can provide information regarding genetic similarities between an arbitrary number of samples, validate specific variants as well as define functionally similar variant groups for further downstream analyses. Its ease of use, installation, complete data-to-conclusions functionality and the inherent flexibility of the R programming language make seqCAT a powerful tool for variant analyses compared to already existing solutions. A publicly available dataset of liver cancer-derived organoids is analysed herein using the seqCAT package, corroborating the original authors' conclusions that the organoids are genetically stable. A previously known liver cancer-related mutation is additionally shown to be present in a sample though it was not listed in the original publication. Differences between DNA- and RNA-based variant calls in this dataset are also analysed revealing a high median concordance of 97.5%. SeqCAT is an open source software under a MIT licence available at https://bioconductor.org/packages/release/bioc/html/seqCAT.html.

A Fluorescent High Throughput Method To Identify Potential Skin Sensitizers

Planta Medica ◽  
2016 ◽  
Vol 82 (05) ◽  
Author(s):  
C Avonto ◽  
AG Chittiboyina ◽  
D Rua ◽  
IA Khan
Keyword(s):  
High Throughput ◽  
High Throughput Method

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

scholarly journals A high-throughput screening method for evolving a demethylase enzyme with improved and new functionalities

2020 ◽  
Author(s):  
Yuru Wang ◽  
Christopher D Katanski ◽  
Christopher Watkins ◽  
Jessica N Pan ◽  
Qing Dai ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Screening Method ◽  
Targeted Mutagenesis ◽  
Rna Repair ◽  
Dna And Rna ◽  
Modified Dna ◽  
Dna Substrates ◽  
Trna Sequencing

Abstract AlkB is a DNA/RNA repair enzyme that removes base alkylations such as N1-methyladenosine (m1A) or N3-methylcytosine (m3C) from DNA and RNA. The AlkB enzyme has been used as a critical tool to facilitate tRNA sequencing and identification of mRNA modifications. As a tool, AlkB mutants with better reactivity and new functionalities are highly desired; however, previous identification of such AlkB mutants was based on the classical approach of targeted mutagenesis. Here, we introduce a high-throughput screening method to evaluate libraries of AlkB variants for demethylation activity on RNA and DNA substrates. This method is based on a fluorogenic RNA aptamer with an internal modified RNA/DNA residue which can block reverse transcription or introduce mutations leading to loss of fluorescence inherent in the cDNA product. Demethylation by an AlkB variant eliminates the blockage or mutation thereby restores the fluorescence signals. We applied our screening method to sites D135 and R210 in the Escherichia coli AlkB protein and identified a variant with improved activity beyond a previously known hyperactive mutant toward N1-methylguanosine (m1G) in RNA. We also applied our method to O6-methylguanosine (O6mG) modified DNA substrates and identified candidate AlkB variants with demethylating activity. Our study provides a high-throughput screening method for in vitro evolution of any demethylase enzyme.

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