scholarly journals AcrIIA5 Suppresses Base Editors and Reduces Their Off-Target Effects

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1786 ◽  
Author(s):  
Mingming Liang ◽  
Tingting Sui ◽  
Zhiquan Liu ◽  
Mao Chen ◽  
Hongmei Liu ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Nuclease Activity ◽  
Inhibitory Effect ◽  
Great Promise ◽  
Genetic Changes ◽  
Base Editing ◽  
Precise Control ◽  
Wide Range ◽  
First Time ◽  
Target Effects

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 changes in a wide range of organisms. These base editors hold great promise for correcting pathogenic mutations and for being used for therapeutic applications. However, the recognition of cognate DNA sequences near their target sites can cause severe off-target effects that greatly limit their clinical applications, and this is an urgent problem that needs to be resolved for base editing systems. The recently discovered phage-derived proteins, anti-CRISPRs, which can suppress the natural CRISPR nuclease activity, may be able to ameliorate the off-target effects of base editing systems. Here, we confirm for the first time that AcrIIA2, AcrIIA4, and AcrIIA5 efficiently inhibit base editing systems in human cells. In particular, AcrIIA5 has a significant inhibitory effect on all base editing variant systems tested in our study. We further show that the off-target effects of BE3 and ABE7.10 were significantly reduced in AcrIIA5 treated cells. This study suggests that AcrIIA5 should be widely used for the precise control of base editing and to thoroughly “shut off” nuclease activity of both CBE and ABE systems.

scholarly journals CRISPR base editors: genome editing without double-stranded breaks

2018 ◽  
Vol 475 (11) ◽  
pp. 1955-1964 ◽  
Author(s):  
Ayman Eid ◽  
Sahar Alshareef ◽  
Magdy M. Mahfouz
Keyword(s):  
Genome Editing ◽  
Dna Sequences ◽  
Genetic Diseases ◽  
Great Promise ◽  
Cytidine Deaminases ◽  
Strand Breaks ◽  
Base Editing ◽  
Potential Applications ◽  
Short Palindromic Repeat ◽  
Basic Biology

The CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 adaptive immunity system has been harnessed for genome editing applications across eukaryotic species, but major drawbacks, such as the inefficiency of precise base editing and off-target activities, remain. A catalytically inactive Cas9 variant (dead Cas9, dCas9) has been fused to diverse functional domains for targeting genetic and epigenetic modifications, including base editing, to specific DNA sequences. As base editing does not require the generation of double-strand breaks, dCas9 and Cas9 nickase have been used to target deaminase domains to edit specific loci. Adenine and cytidine deaminases convert their respective nucleotides into other DNA bases, thereby offering many possibilities for DNA editing. Such base-editing enzymes hold great promise for applications in basic biology, trait development in crops, and treatment of genetic diseases. Here, we discuss recent advances in precise gene editing using different platforms as well as their potential applications in basic biology and biotechnology.

scholarly journals A qualitative study of the nodulating ability of legumes of Pakistan

2014 ◽  
Vol 66 (3-4) ◽  
pp. 387-391
Author(s):  
Mohammad Athar
Keyword(s):  
Garden Soil ◽  
Great Promise ◽  
Soil Conditions ◽  
Natural Soil ◽  
Agricultural Ecosystem ◽  
Rhizobial Inoculation ◽  
Wide Range ◽  
Wild Legumes ◽  
Mineralizable Nitrogen ◽  
First Time

<em>Legume-Rhizobium</em> symbiosis accumulates substantial amounts of mineralizable nitrogen which help in ecological rehabilitation of degraded soils and increase the soil fertility in agricultural ecosystem. Nodulation was studied in 72 legume species from various parts of Pakistan. All the species of <em>Papilionoideae</em> and <em>Mimosoideae</em> were nodulated whereas all the species examined in <em>Caesalpinioideae</em> were non-nodulated. Attempts to elicit nodulation in <em>Caesalpinioid</em> species by rhizobial inoculation were not successful and they were accepted as lacking nodulating ability. Nodulation is reported for the first time in 6 species within 3 genera of <em>Mimosoideae</em> and 9 species within 5 genera of <em>Papilionoideae</em>. Majority of the species were abundantly nodulated under natural soil conditions or when grown in uninoculated garden soil indicating distribution of wide range of naturalized rhizobia. The study shows that the wild legumes hold great promise for inclusion in revegetation of denuded and derelict ecosystems.

scholarly journals Base editing generates substantial off-target single nucleotide variants

2018 ◽  
Author(s):  
Erwei Zuo ◽  
Yidi Sun ◽  
Wu Wei ◽  
Tanglong Yuan ◽  
Wenqin Ying ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biomedical Application ◽  
Spontaneous Mutation ◽  
Great Promise ◽  
Single Nucleotide Variants ◽  
Spontaneous Mutation Rate ◽  
Single Nucleotide ◽  
Base Editing ◽  
Genome Wide ◽  
Target Effects

AbstractGenome editing tools including CRISPR/Cas9 and base editors hold great promise for correcting pathogenic mutations. Unbiased genome-wide off-target effects of the editing in mammalian cells is required before clinical applications, but determination of the extent of off-target effects has been difficult due to the existence of single nucleotide polymorphisms (SNPs) in individuals. Here, we developed a method named GOTI (Genome-wide Off-target analysis by Two-cell embryo Injection) to detect off-target mutations without interference of SNPs. We applied GOTI to both the CRISPR-Cas9 and base editing (BE3) systems by editing one blastomere of the two-cell mouse embryo and then compared whole genome sequences of progeny-cell populations at E14.5 stage. Sequence analysis of edited and non-edited cell progenies showed that undesired off-target single nucleotide variants (SNVs) are rare (average 10.5) in CRISPR-edited mouse embryos, with a frequency close to the spontaneous mutation rate. By contrast, BE3 editing induced over 20-fold higher SNVs (average 283), raising the concern of using base-editing approaches for biomedical application.

Notes on the genus Leveillula (Erysiphaceae): a new unrecorded species and notes on Leveillula infecting Ficus, Cucurbita and Tropaeolum in Iran

Phytotaxa ◽  
2016 ◽  
Vol 260 (3) ◽  
pp. 267 ◽  
Author(s):  
SEYED AKBAR KHODAPARAST ◽  
SUSUMU TAKAMATSU ◽  
ADEL SHADLOU ◽  
MOHSEN DAMADI ◽  
MAHDI PIRNIA ◽  
...  
Keyword(s):  
Powdery Mildew ◽  
Dna Sequences ◽  
Common Species ◽  
Its Sequences ◽  
Ficus Carica ◽  
Warm Climate ◽  
Rdna Its ◽  
Wide Range ◽  
Rdna Its Sequences ◽  
First Time

Taxonomy of the genus Leveillula has long been considered as a challenge in powdery mildew systematics. During the last decade the rDNA diversity has been used for phylogenetic analysis of the genus Leveillula aiming for better understanding of the genetic diversity and taxonomy of the genus. Iran with an arid and warm climate provides a high Leveillula powdery mildew diversity associated with a wide range of host plants. In this study we have obtained additional rDNA ITS sequences from four samples which show more diversity on ITS rDNA region. According to our observation morphology of Leveillula on Tropaeolum majus is different from what described as L. tropaeolicola on this host species. Leveillula on Ficus carica could be closely related to L. contractirostris. The fungus on Cucurbita is morphologically different from L. taurica, a common species that has been recorded on a wide range of crops as well as Cucurbitaceae. To determine phylogenetic relationships and to facilitate species identification, ITS regions of rDNA were sequenced for new collections. Sequence of rDNA ITS from Cucurbita powdery mildew showed 100% identity to those of L. thevenotiae. Leveillula on Ficus carica clustered with L. contractirostris. ITS sequences of L. jaczewskii was generated for the first time. These data showed that L. jaczewskii is closely related to L. taurica on Zygophyllum fabago (holotype host for L. taurica), however, the two DNA sequences differ at five positions.

Safety assessment of biological raw materials in the system of medicines quality assurance

2020 ◽  
pp. 63-72
Author(s):  
Yu. Olefir ◽  
E. Sakanyan ◽  
I. Osipova ◽  
V. Dobrynin ◽  
M. Smirnova ◽  
...  
Keyword(s):  
Raw Materials ◽  
State Level ◽  
The State ◽  
Spongiform Encephalopathy ◽  
Safety Standards ◽  
Wide Range ◽  
The Russian Federation ◽  
Key Aspects ◽  
First Time ◽  
Medicines Quality

The entry of a wide range of biotechnological products into the pharmaceutical market calls for rein-forcement of the quality, efficacy and safety standards at the state level. The following general monographs have been elaborated for the first time to be included into the State Pharmacopoeia of the Russian Federation, XIV edition: "Viral safety" and "Reduction of the risk of transmitting animal spongiform encephalopathy via medicinal products". These general monographs were elaborated taking into account the requirements of foreign pharmacopoeias and the WHO recommendations. The present paper summarises the key aspects of the monographs.

Phytochemical evaluation of leaf extracts of Naringi crenulata (roxb.) Nicolson

2016 ◽  
Vol 5 (11) ◽  
pp. 5110
Author(s):  
Sartaj Ahmad Allayie ◽  
Mushtaq Ahmed Parray* ◽  
Bilal Ahmad Bhat ◽  
S. Hemalatha
Keyword(s):  
Quantitative Analysis ◽  
Solvent System ◽  
Great Promise ◽  
Phytochemical Analysis ◽  
Bioactive Constituents ◽  
Leaf Extracts ◽  
Traditional Medicines ◽  
The People ◽  
Wide Range ◽  
Rf Values

The use of traditional medicines holds a great promise as an easily available source as effective medicinal agents to cure a wide range of ailments among the people particularly in tropical developing countries like India. The present study investigates the qualitative and quantitative analysis of the major bioactive constituents of N. crenulata leaf extracts. The extractive values of aqueous, acetone and chloroform extracts were found to be 11.34, 4.24 and 6.06 respectively. Qualitative phytochemical analysis of these three solvent extracts confirm the presence of Alkaloids, Saponins, Flavonoids and Phenolic compounds in all the three extracts; however, these phytochemicals were more significant in aqueous extract. Quantitative analysis was carried out using TLC method by different solvent system. Amongst various solvent systems, Butanol: acetic acid: water (9: 0.9: 0.1 v/v/v) shows maximum resolution and number of spots produced at long UV (365 nm) and under iodine vapours. The TLC chromatograms constituted different coloured phytochemical compounds with different Rf values. It can be conveniently used to evaluate the quality of different area samples. This indicates that the leaves can be useful for treating different diseases because the therapeutic activity of a plant is due to the presence of particular class of compounds and thus can serve as potential sources of useful drugs in future.

Innovation in Byzantine Medicine

2020 ◽  
Author(s):  
Petros Bouras-Vallianatos
Keyword(s):  
Human Physiology ◽  
Medical Literature ◽  
Cultural Exchange ◽  
Significant Degree ◽  
Medieval Medicine ◽  
Medieval Latin ◽  
Main Thesis ◽  
Wide Range ◽  
Comprehensive Examination ◽  
First Time

Byzantine medicine is still a little-known and misrepresented field not only in the wider arena of debates on medieval medicine but also among Byzantinists. Byzantine medical literature is often viewed as ‘stagnant’ and mainly preserving ancient ideas; and our knowledge of it continues to be based to a great extent on the comments of earlier authorities, which are often repeated uncritically. This book presents the first comprehensive examination of the medical corpus of, arguably, the most important late Byzantine physician John Zacharias Aktouarios (c.1275–c.1330). The main thesis is that John’s medical works show an astonishing degree of openness to knowledge from outside Byzantium combined with a significant degree of originality, in particular, in the fields of uroscopy, pharmacology, and human physiology. The analysis of John’s edited (On Urines and On Psychic Pneuma) and unedited (Medical Epitome) works is supported for the first time by the consultation of a large number of manuscripts. The study is also informed by evidence from a wide range of medical sources, including previously unpublished ones, and texts from other genres, such as epistolography and merchants’ accounts. The contextualization of John’s works sheds new light on the development of Byzantine medical thought and practice, and enhances our understanding of the late Byzantine social and intellectual landscape. Finally, John’s medical observations are also examined in the light of examples from the medieval Latin and Islamic worlds, placing his medical theories in the wider Mediterranean milieu and highlighting the cultural exchange between Byzantium and its neighbours.

Rebels, Believers, Survivors

2020 ◽  
Author(s):  
Noel Malcolm
Keyword(s):  
Catholic Church ◽  
Religious Conversion ◽  
Late Nineteenth Century ◽  
Napoleonic Wars ◽  
Conversion To Islam ◽  
Wide Range ◽  
History Of ◽  
External Powers ◽  
First Time ◽  
Modern Myth

This book of essays covers a wide range of topics in the history of Albania and Kosovo. Many of the essays illuminate connections between the Albanian lands and external powers and interests, whether political, military, diplomatic or religious. Such topics include the Habsburg invasion of Kosovo in 1689, the manoeuvrings of Britain and France towards the Albanian lands during the Napoleonic Wars, the British interest in those lands in the late nineteenth century, and the Balkan War of 1912. On the religious side, essays examine ‘crypto-Christianity’ in Kosovo during the Ottoman period, the stories of conversion to Islam revealed by Inquisition records, the first theological treatise written in Albanian (1685), and the work of the ‘Apostolic Delegate’ who reformed the Catholic Church in early twentieth-century Albania. Some essays bring to life ordinary individuals hitherto unknown to history: women hauled before the Inquisition, for example, or the author of the first Albanian autobiography. The longest essay, on Ali Pasha, tells for the first time the full story of the role he played in the international politics of the Napoleonic Wars. Some of these studies have been printed before (several in hard-to-find publications, and one only in Albanian), but the greater part of this book appears here for the first time. This is not only a contribution to Albanian and Balkan history it also engages with many broader issues, including religious conversion, methods of enslavement within the Ottoman Empire, and the nature of modern myth-making about national identity.

Recycling and Reuse in the Roman Economy

2020 ◽  
Keyword(s):  
Building Materials ◽  
Computational Modelling ◽  
Late Antique ◽  
Roman Economy ◽  
Wide Range ◽  
The Status ◽  
Recent Developments ◽  
Methodological Approaches ◽  
First Time ◽  
Site Types

The recycling and reuse of materials and objects were extensive in the past, but have rarely been embedded into models of the economy; even more rarely has any attempt been made to assess the scale of these practices. Recent developments, including the use of large datasets, computational modelling, and high-resolution analytical chemistry, are increasingly offering the means to reconstruct recycling and reuse, and even to approach the thorny matter of quantification. Growing scholarly interest in the topic has also led to an increasing recognition of these practices from those employing more traditional methodological approaches, which are sometimes coupled with innovative archaeological theory. Thanks to these efforts, it has been possible for the first time in this volume to draw together archaeological case studies on the recycling and reuse of a wide range of materials, from papyri and textiles, to amphorae, metals and glass, building materials and statuary. Recycling and reuse occur at a range of site types, and often in contexts which cross-cut material categories, or move from one object category to another. The volume focuses principally on the Roman Imperial and late antique world, over a broad geographical span ranging from Britain to North Africa and the East Mediterranean. Last, but not least, the volume is unique in focusing upon these activities as a part of the status quo, and not just as a response to crisis.

scholarly journals A Virtual Telescope for the Open University Science Foundation Course

1998 ◽  
Vol 162 ◽  
pp. 100-105
Author(s):  
Andrew J. Norton ◽  
Mark H. Jones
Keyword(s):  
Social Science ◽  
Open University ◽  
Distance Teaching ◽  
The Arts ◽  
Wide Range ◽  
University Science ◽  
First Time ◽  
Degree Level ◽  
Selection Of

The Open University is the UK's foremost distance teaching university. For over twenty five years we have been presenting courses to students spanning a wide range of degree level and vocational subjects. Since we have no pre-requisites for entry, a major component of our course profile is a selection of foundation courses comprising one each in the Arts, Social Science, Mathematics, Technology and Science faculties. The Science Faculty's foundation course is currently undergoing a substantial revision. The new course, entitled “S103: Discovering Science”, will be presented to students for the first time in 1998.

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