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MIT, Broad scientists overcome key CRISPR-Cas9 genome editing hurdle
Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR-Cas9 genome editing system that significantly cut down on “off-target” editing errors. The refined technique addresses one of the major technical issues in the use of genome editing.
The CRISPR-Cas9 system works by making a precisely targeted modification in a cell's DNA. The protein Cas9 alters the DNA at a location that is specified by a short RNA whose sequence matches that of the target site. While Cas9 is known to be highly efficient at cutting its target site, a major drawback of the system has been that, once inside a cell, it can bind to and cut additional sites that are not targeted. This has the potential to produce undesired edits that can alter gene expression or knock a gene out entirely, which might lead to the development of cancer or other problems.
In a paper published today in Science, Feng Zhang and his colleagues report that changing three of the approximately 1,400 amino acids that make up the Cas9 enzyme from S. pyogenes dramatically reduced “off-target editing” to undetectable levels in the specific cases examined. Zhang is the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s departments of Brain and Cognitive Sciences and Biological Engineering, and a member of both the Broad Institute and McGovern Institute.
Zhang and his colleagues used knowledge about the structure of the Cas9 protein to decrease off-target cutting. DNA, which is negatively charged, binds to a groove in the Cas9 protein that is positively charged. Knowing the structure, the scientists were able to predict that replacing some of the positively charged amino acids with neutral ones would decrease the binding of “off target” sequences much more than “on target” sequences.
After experimenting with various possible changes, Zhang’s team found that mutations in three amino acids dramatically reduced “off-target” cuts. For the guide RNAs tested, “off-target” cutting was so low as to be undetectable.
The newly-engineered enzyme, which the team calls “enhanced” S. pyogenes Cas9, or eSpCas9, will be useful for genome editing applications that require a high level of specificity. The Zhang Lab is immediately making the eSpCas9 enzyme available for researchers worldwide. The team believes the same charge-changing approach will work with other recently described RNA-guided DNA targeting enzymes, including Cpf1, C2C1, and C2C3, which Zhang and his collaborators reported on earlier this year.
The prospect of rapid and efficient genome editing raises many ethical and societal concerns, says Zhang, who is speaking this morning at the International Summit on Gene Editing in Washington. “Many of the safety concerns are related to off-target effects,” he says. “We hope the development of eSpCas9 will help address some of those concerns, but we certainly don’t see this as a magic bullet. The field is advancing at a rapid pace, and there is still a lot to learn before we can consider applying this technology for clinical use.”
Source: http://news.mit.edu/2015/overcome-crispr-cas9-genome-editing-hurdle-1201
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Founded by Russian entrepreneur Dmitry Itskov in February 2011 with the participation of leading Russian specialists in the field of neural interfaces, robotics, artificial organs and systems.
The main goals of the 2045 Initiative: the creation and realization of a new strategy for the development of humanity which meets global civilization challenges; the creation of optimale conditions promoting the spiritual enlightenment of humanity; and the realization of a new futuristic reality based on 5 principles: high spirituality, high culture, high ethics, high science and high technologies.
The main science mega-project of the 2045 Initiative aims to create technologies enabling the transfer of a individual’s personality to a more advanced non-biological carrier, and extending life, including to the point of immortality. We devote particular attention to enabling the fullest possible dialogue between the world’s major spiritual traditions, science and society.
A large-scale transformation of humanity, comparable to some of the major spiritual and sci-tech revolutions in history, will require a new strategy. We believe this to be necessary to overcome existing crises, which threaten our planetary habitat and the continued existence of humanity as a species. With the 2045 Initiative, we hope to realize a new strategy for humanity's development, and in so doing, create a more productive, fulfilling, and satisfying future.
The "2045" team is working towards creating an international research center where leading scientists will be engaged in research and development in the fields of anthropomorphic robotics, living systems modeling and brain and consciousness modeling with the goal of transferring one’s individual consciousness to an artificial carrier and achieving cybernetic immortality.
An annual congress "The Global Future 2045" is organized by the Initiative to give platform for discussing mankind's evolutionary strategy based on technologies of cybernetic immortality as well as the possible impact of such technologies on global society, politics and economies of the future.
Future prospects of "2045" Initiative for society
2015-2020
The emergence and widespread use of affordable android "avatars" controlled by a "brain-computer" interface. Coupled with related technologies “avatars’ will give people a number of new features: ability to work in dangerous environments, perform rescue operations, travel in extreme situations etc.
Avatar components will be used in medicine for the rehabilitation of fully or partially disabled patients giving them prosthetic limbs or recover lost senses.
2020-2025
Creation of an autonomous life-support system for the human brain linked to a robot, ‘avatar’, will save people whose body is completely worn out or irreversibly damaged. Any patient with an intact brain will be able to return to a fully functioning bodily life. Such technologies will greatly enlarge the possibility of hybrid bio-electronic devices, thus creating a new IT revolution and will make all kinds of superimpositions of electronic and biological systems possible.
2030-2035
Creation of a computer model of the brain and human consciousness with the subsequent development of means to transfer individual consciousness onto an artificial carrier. This development will profoundly change the world, it will not only give everyone the possibility of cybernetic immortality but will also create a friendly artificial intelligence, expand human capabilities and provide opportunities for ordinary people to restore or modify their own brain multiple times. The final result at this stage can be a real revolution in the understanding of human nature that will completely change the human and technical prospects for humanity.
2045
This is the time when substance-independent minds will receive new bodies with capacities far exceeding those of ordinary humans. A new era for humanity will arrive! Changes will occur in all spheres of human activity – energy generation, transportation, politics, medicine, psychology, sciences, and so on.
Today it is hard to imagine a future when bodies consisting of nanorobots will become affordable and capable of taking any form. It is also hard to imagine body holograms featuring controlled matter. One thing is clear however: humanity, for the first time in its history, will make a fully managed evolutionary transition and eventually become a new species. Moreover, prerequisites for a large-scale expansion into outer space will be created as well.
Key elements of the project in the future
• International social movement
• social network immortal.me
• charitable foundation "Global Future 2045" (Foundation 2045)
• scientific research centre "Immortality"
• business incubator
• University of "Immortality"
• annual award for contribution to the realization of the project of "Immortality”.
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