DNA Editing: A Primer

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-16-SCI-16
Author(s):  
Prashant Mali
Keyword(s):  
Genome Engineering ◽  
Conflicts Of Interest ◽  
Cellular Organization ◽  
Dna Editing ◽  
Tools And Techniques ◽  
And Behavior

Abstract RNA-guided Cas9 nucleases based on the prokaryotic CRISPR-Cas systems provide an unprecedented ease in being able to edit the genomes of diverse organisms. As a single unifying factor capable of co-localizing RNA, DNA, and protein, I believe tools and techniques based on Cas9 will grant exquisite control over cellular organization, regulation, and behavior. Here I will describe work on development of the CRISPR-Cas9 targeting methodology, and detail current and prospective genome-engineering methodologies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Industry Payment to Vascular Neurologists

Stroke ◽  
2020 ◽  
Vol 51 (4) ◽  
pp. 1339-1343 ◽  
Author(s):  
Krishna Nalleballe ◽  
Sen Sheng ◽  
Chenghui Li ◽  
Ruchira Mahashabde ◽  
Amarnath R. Annapureddy ◽  
...  
Keyword(s):  
United States ◽  
Clinical Practice ◽  
American Heart Association ◽  
American Heart ◽  
Conflicts Of Interest ◽  
Heart Association ◽  
The United States ◽  
Regional Trends ◽  
Impact Patient Care ◽  
And Behavior

Background and Purpose— Industry payments to physicians raise concerns regarding conflicts of interest that could impact patient care. We explored nonresearch and nonownership payments from industry to vascular neurologists to identify trends in compensation. Methods— Using Centers for Medicare and Medicaid Services and American Board of Psychiatry and Neurology data, we explored financial relationships between industry and US vascular neurologists from 2013 to 2018. We analyzed payment characteristics, including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Furthermore, we analyzed the top 1% (by compensation) of vascular neurologists with detailed payment categories, their position, and their contribution to stroke guidelines. Results— The number of board certified vascular neurologist increased from 1169 in 2013 to 1746 in 2018. The total payments to vascular neurologist increased from $99 749 in 2013 to $1 032 302 in 2018. During the study period, 16% to 17% of vascular neurologists received industry payments. Total payments from industry and mean physician payments increased yearly over this period, with consulting fee (31.1%) and compensation for services other than consulting (30.7%) being the highest paid categories. The top 10 manufacturers made the majority of the payments, and the top 10 products changed from drug or biological products to devices. Physicians from south region of the United States received the highest total payment (38.72%), which steadily increased. Payments to top 1% vascular neurologists increased from 64% to 79% over the period as payments became less evenly distributed. Among the top 1%, 42% specialized in neuro intervention, 11% contributed to American Heart Association/American Stroke Association guidelines, and around 75% were key leaders in the field. Conclusions— A small proportion of US vascular neurologists consistently received the majority of industry payments, the value of which grew over the study period. Only 11% of the top 1% receiving industry payments have authored American Heart Association/American Stroke Association guidelines, but ≈75% seem to be key leaders in the field. Whether this influences clinical practice and behavior requires further investigation.

scholarly journals A genome engineering resource to uncover principles of cellular organization and tissue architecture by lipid signalling

2020 ◽  
Author(s):  
Deepti Trivedi ◽  
Vinitha CM ◽  
Karishma Bisht ◽  
Vishnu Janardan ◽  
Awadhesh Pandit ◽  
...  
Keyword(s):  
Human Disease ◽  
Genome Engineering ◽  
Cultured Cells ◽  
Cellular Organization ◽  
Cellular Processes ◽  
Lipid Signalling ◽  
Disease Biology ◽  
A Genome ◽  
Biochemical Analyses

SummaryPhosphoinositides (PI) are key regulators of cellular organization in eukaryotes and genes that tune PI signalling are implicated in human disease mechanisms. Biochemical analyses and studies in cultured cells have identified a large number of proteins that can mediate PI signalling. However, the role of such proteins in regulating cellular processes in vivo and development in metazoans remains to be understood. Here we describe a set of CRISPR based genome engineering tools that allow the manipulation of each of these proteins with spatial and temporal control during metazoan development. We demonstrate the use of these reagents to deplete a set of 103 proteins individually in the Drosophila eye and identify several new molecules that control eye development. Our work demonstrates the power of this resource in uncovering the molecular basis of tissue homeostasis during normal development and in human disease biology.

scholarly journals MagnEdit—interacting factors that recruit DNA-editing enzymes to single base targets

2020 ◽  
Vol 3 (4) ◽  
pp. e201900606 ◽  
Author(s):  
Jennifer L McCann ◽  
Daniel J Salamango ◽  
Emily K Law ◽  
William L Brown ◽  
Reuben S Harris
Keyword(s):  
Genome Engineering ◽  
Gene Knockout ◽  
Target Site ◽  
Proof Of Concept ◽  
Interacting Protein ◽  
Single Base ◽  
Minimal Damage ◽  
Dna Editing ◽  
Editing Enzyme ◽  
Lower Frequencies

Although CRISPR/Cas9 technology has created a renaissance in genome engineering, particularly for gene knockout generation, methods to introduce precise single base changes are also highly desirable. The covalent fusion of a DNA-editing enzyme such as APOBEC to a Cas9 nickase complex has heightened hopes for such precision genome engineering. However, current cytosine base editors are prone to undesirable off-target mutations, including, most frequently, target-adjacent mutations. Here, we report a method to “attract” the DNA deaminase, APOBEC3B, to a target cytosine base for specific editing with minimal damage to adjacent cytosine bases. The key to this system is fusing an APOBEC-interacting protein (not APOBEC itself) to Cas9n, which attracts nuclear APOBEC3B transiently to the target site for editing. Several APOBEC3B interactors were tested and one, hnRNPUL1, demonstrated proof-of-concept with successful C-to-T editing of episomal and chromosomal substrates and lower frequencies of target-adjacent events.

scholarly journals Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Minh Thuan Nguyen Tran ◽  
Mohd Khairul Nizam Mohd Khalid ◽  
Qi Wang ◽  
Jacqueline K. R. Walker ◽  
Grace E. Lidgerwood ◽  
...  
Keyword(s):  
Genome Engineering ◽  
Editing Efficiency ◽  
Base Editing ◽  
Target Dna ◽  
Dna Editing ◽  
Target Activity ◽  
Adenine Base

Abstract Precision genome engineering has dramatically advanced with the development of CRISPR/Cas base editing systems that include cytosine base editors and adenine base editors (ABEs). Herein, we compare the editing profile of circularly permuted and domain-inlaid Cas9 base editors, and find that on-target editing is largely maintained following their intradomain insertion, but that structural permutation of the ABE can affect differing RNA off-target events. With this insight, structure-guided design was used to engineer an SaCas9 ABE variant (microABE I744) that has dramatically improved on-target editing efficiency and a reduced RNA-off target footprint compared to current N-terminal linked SaCas9 ABE variants. This represents one of the smallest AAV-deliverable Cas9-ABEs available, which has been optimized for robust on-target activity and RNA-fidelity based upon its stereochemistry.

Dynamic interplay between interfacial nanobubbles: Oversaturation promotes anisotropic depinning and bubble coalescence

2021 ◽  
Author(s):  
Sarthak Nag ◽  
Yoko Tomo ◽  
Hideaki Teshima ◽  
Koji Takahashi ◽  
Masamichi Kohno
Keyword(s):  
Bubble Coalescence ◽  
Tools And Techniques ◽  
And Behavior ◽  
Dynamic Interplay

Probing the nanobubbles’ dynamics is essential to understand their longevity and behavior. Importantly, such observation requires tools and techniques having high temporal resolutions to capture nanobubble’s intrinsic characteristics. In this...

scholarly journals THE INNOVATION-ENTREPRENEURIAL MODELS IN TRANSFER OF ACADEMIC TECHNOLOGIES: TRANSFORMATION OF VALUATIONAL ENTITY AND CONTRADICTIONS OF REALIZATION

2020 ◽  
pp. 33-41
Author(s):  
I. Novikova
Keyword(s):  
Technology Transfer ◽  
Technology Implementation ◽  
Conflicts Of Interest ◽  
Innovation Process ◽  
Economic Relationships ◽  
Technological Transfer ◽  
Circular Model ◽  
Academic Technology ◽  
Knowledge Intensive ◽  
And Behavior

The evolution of the transformation of the essence of the main innovation-entrepreneurial models in technological transfer is analyzed. It is shown that the emergence of new models of technology transfer is caused by: new forms of competition, changes in public requests and needs, choice of the way of technology implementation, the need to increase revenue, etc. It was found that the modern content of technology transfer models was formed on the basis of previous theories, which directly or indirectly took into account: interests of the research industry, consumer requests and behavior, state priorities and peculiarities of economic relationships between all subjects of the innovation process. Chronological systematization of the main innovative-entrepreneurial models in technology transfer has been carried out. The strengths and weaknesses of the major models of technological transfer are identified, as well as the importance of strategic planning in implementing the process of academic technology transfer. It is proven that modeling in a knowledge-intensive business is able to help solve many common problems that are now encountered in commercial technology transfer. The potential of activating technological transfer in research universities through the lens of the concept of “open” innovations by H. Chesbrough is revealed. The risks and probable conflicts of interest of this concept have been identified. The advantages of the circular model of technology transfer are analyzed. The strategic mistakes made in the science-intensive business are shown.

scholarly journals How Do People Search Information on Content and Sources? Integrating Source Search in Information Boards

2021 ◽  
Author(s):  
Leonie Aßmann ◽  
Holger Futterleib ◽  
Tilmann Betsch ◽  
Eva Thomm ◽  
Johannes Bauer
Keyword(s):  
Information Search ◽  
Conflicts Of Interest ◽  
Source Information ◽  
Prior Beliefs ◽  
Educational Domain ◽  
Standard Information ◽  
People Search ◽  
Information Board ◽  
And Behavior ◽  
Content Information

Information forms the basis for beliefs, judgements, decision making, and behavior. Nowadays, the amount of information available is continually increasing. Still, the quality and credibility of the corresponding sources vary widely. Thus, to avoid making judgments and decisions on basis of biased information, the credibility of information and sources must be carefully evaluated. However, information regarding the source is often not immediately accessible and, instead, must be purposefully sought. The standard information board paradigm does not include such a source information search. Therefore, we investigated whether that paradigm can be extended with an active search of source information in order to investigate search behaviors with regard to content und source information. To do so, we presented participants with information boards on different topics from two domains (i.e., health and education). The boards contained a question to outline the topic of information search in addition to four related sources. For each source, we provided information on topic-related expertise and potential conflicts of interest as well as content information regarding the question (i.e., pro and contra arguments). Information was hidden so that participants had to actively search the information. We were interested in the search start, search amount, differences in search between the domains and belief revision due to information search. Results show that participants primarily began information search with source expertise before continuing on to content information. In general, both content and source information were searched. Domain did not influence the start but the search amount⎯more information was searched on topics in the educational domain. In addition, search appeared to influence prior beliefs. For some topics, we observed changes in beliefs following information search.The findings indicate that our variations in the information board paradigm can be used to investigate content information search and source information search simultaneously.

The Evolution of Function and Behavior During Mechanical Design

1993 ◽  
Author(s):  
David G. Ullman
Keyword(s):  
Design Process ◽  
Mechanical Design ◽  
Design Rationale ◽  
Design History ◽  
Academic Interest ◽  
Computer Based ◽  
Tools And Techniques ◽  
And Behavior

Abstract This paper explores the meaning and evolution of function and behavior during mechanical design. The paper is based on an example from practice. The goal is to develop a model of the information developed during the design process and thus define the types of data inherent in mechanical design. Beyond the academic interest of defining function and behavior, this work is important to the development of representations for computer based design history and design rationale tools and techniques.

Sign in / Sign up

Export Citation Format

Share Document