Gene editing gets safer thanks to redesigned Cas9 protein

Science Daily

Originally posted 2 MAR 22

Summary:

Scientists have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

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Scientists have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

One of the grand challenges with using CRISPR-based gene editing on humans is that the molecular machinery sometimes makes changes to the wrong section of a host's genome, creating the possibility that an attempt to repair a genetic mutation in one spot in the genome could accidentally create a dangerous new mutation in another.

But now, scientists at The University of Texas at Austin have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer. The work is described in a paper published today in the journal Nature.

"This really could be a game changer in terms of a wider application of the CRISPR Cas systems in gene editing," said Kenneth Johnson, a professor of molecular biosciences and co-senior author of the study with David Taylor, an assistant professor of molecular biosciences. The paper's co-first authors are postdoctoral fellows Jack Bravo and Mu-Sen Liu.

The info is here.

Journal Reference:

Jack P. K. Bravo, Mu-Sen Liu, et al. Structural basis for mismatch surveillance by CRISPR–Cas9. Nature, 2022; DOI: 10.1038/s41586-022-04470-1

What Is Prudent Governance of Human Genome Editing?

Scott J. Schweikart
AMA J Ethics. 2019;21(12):E1042-1048.
doi: 10.1001/amajethics.2019.1042.

Abstract

CRISPR technology has made questions about how best to regulate human genome editing immediately relevant. A sound and ethical governance structure for human genome editing is necessary, as the consequences of this new technology are far-reaching and profound. Because there are currently many risks associated with genome editing technology, the extent of which are unknown, regulatory prudence is ideal. When considering how best to create a prudent governance scheme, we can look to 2 guiding examples: the Asilomar conference of 1975 and the German Ethics Council guidelines for human germline intervention. Both models offer a path towards prudent regulation in the face of unknown and significant risks.

Here is an excerpt:

Beyond this key distinction, the potential risks and consequences—both to individuals and society—of human genome editing are relevant to ethical considerations of nonmaleficence, beneficence, justice, and respect for autonomy and are thus also relevant to the creation of an appropriate regulatory model. Because genome editing technology is at its beginning stages, it poses safety risks, the off-target effects of CRISPR being one example. Another issue is whether gene editing is done for therapeutic or enhancement purposes. While either purpose can prove beneficial, enhancement has potential for abuse.
Moreover, concerns exist that genome editing for enhancement can thwart social justice, as wealthy people will likely have greater ability to enhance their genome (and thus presumably certain physical and mental characteristics), furthering social and class divides. With regards to germline editing, a relevant concern is how, during the informed consent process, to respect the autonomy of persons in future generations whose genomes are modified before birth. The questions raised by genome editing are profound, and the risks—both to the individual and to society—are evident. Left without proper governance, significant harmful consequences are possible.

The info is here.

Is Editing the Genome for Climate Change Adaptation Ethically Justifiable?

Lisa Soleymani Lehmann
AMA J Ethics. 2017;19(12):1186-1192.

Abstract

As climate change progresses, we humans might have to inhabit a world for which we are increasingly maladapted. If we were able to identify genes that directly influence our ability to thrive in a changing climate, would it be ethically justifiable to edit the human genome to enhance our ability to adapt to this new environment? Should we use gene editing not only to prevent significant disease but also to enhance our ability to function in the world? Here I suggest a “4-S framework” for analyzing the justifiability of gene editing that includes these considerations: (1) safety, (2) significance of harm to be averted, (3) succeeding generations, and (4) social consequences.

Conclusion

Gene editing has unprecedented potential to improve human health. CRISPR/Cas9 has a specificity and simplicity that opens up wide possibilities. If we are unable to prevent serious negative health consequences of climate change through environmental and public health measures, gene editing could have a role in helping human beings adapt to new environmental conditions. Any decision to proceed should apply the 4-S framework.

The info is here.

The Amazing Ways Artificial Intelligence Is Transforming Genomics and Gene Editing

Bernard Marr
Forbes.com
Originally posted November 16, 2018

Here is an excerpt:

Another thing experts are working to resolve in the process of gene editing is how to prevent off-target effects—when the tools mistakenly work on the wrong gene because it looks similar to the target gene.

Artificial intelligence and machine learning help make gene editing initiatives more accurate, cheaper and easier.

The future for AI and gene technology is expected to include pharmacogenomics, genetic screening tools for newborns, enhancements to agriculture and more. While we can't predict the future, one thing is for sure: AI and machine learning will accelerate our understanding of our own genetic makeup and those of other living organisms.

The info is here.

Japan Set to Allow Gene Editing in Human Embryos

David Cyranoski
Scientific American
Originally posted on October 3, 2018

Japan has issued draft guidelines that allow the use of gene-editing tools in human embryos. The proposal was released by an expert panel representing the country’s health and science ministries on 28 September.

Although the country regulates the use of human embryos for research, there have been no specific guidelines on using tools such as CRISPR–Cas9 to make precise modifications in their DNA until now.

Tetsuya Ishii, a bioethicist at Hokkaido University in Sapporo, says that before the draft guidelines were issued, Japan’s position on gene editing in human embryos was neutral. The proposal now encourages this kind of research, he says.

But if adopted, the guidelines would restrict the manipulation of human embryos for reproduction, although this would not be legally binding.

Manipulating DNA in embryos could reveal insights into early human development. Researchers also hope that in the long term, these tools could be used to fix genetic mutations that cause diseases, before they are passed on.

The info is here.

The Ethics of CRISPR

Noah Robischon
Fast Company
Originally published on June 20, 2017

On the eve of publishing her new book, Jennifer Doudna, a pioneer in the field of CRISPR-Cas9 biology and genome engineering, spoke with Fast Company about the potential for this new technology to be used for good or evil.

“The worst thing that could happen would be for [CRISPR] technology to be speeding ahead in laboratories,” Doudna tells Fast Company. “Meanwhile, people are unaware of the impact that’s coming down the road.” That’s why Doudna and her colleagues have been raising awareness of the following issues.

DESIGNER HUMANS

Editing sperm cells or eggs—known as germline manipulation—would introduce inheritable genetic changes at inception. This could be used to eliminate genetic diseases, but it could also be a way to ensure that your offspring have blue eyes, say, and a high IQ. As a result, several scientific organizations and the National Institutes of Health have called for a moratorium on such experimentation. But, writes Doudna, “it’s almost certain that germline editing will eventually be safe enough to use in the clinic.”

The article is here.

Can Human Evolution Be Controlled?

William B. Hurlbut
Big Questions Online
Originally published February 17, 2017

Here is an excerpt:

These gene-editing techniques may transform our world as profoundly as many of the greatest scientific discoveries and technological innovations of the past — like electricity, synthetic chemistry, and nuclear physics. CRISPR/Cas9 could provide urgent and uncontroversial progress in biomedical science, agriculture, and environmental ecology. Indeed, the power and depth of operation of these new tools is delivering previously unimagined possibilities for reworking or redeploying natural biological processes — some with startling and disquieting implications. Proposals by serious and well-respected scientists include projects of broad ecological engineering, de-extinction of human ancestral species, a biotechnological “cure” for aging, and guided evolution of the human future.

The questions raised by such projects go beyond issues of individual rights and social responsibilities to considerations of the very source and significance of the natural world, its integrated and interdependent processes, and the way these provide the foundational frame for the physical, psychological, and spiritual meaning of human life.

The article is here.

Genome Editing: An Ethical Review

Nuffield Council on Bioethics
Published September 2016

This review considers the impact of recent advances in genome editing, which have diffused rapidly across many fields of biological research, and the range of ethical questions to which they give rise. It was carried out by an interdisciplinary Working Group that included expertise in science, law, philosophy, ethics, sociology and industry. In coming to its conclusions, the Working Group invited contributions from a wide range of people, including through an open call for evidence that ran from November 2015 until February 2016.

The review sets out our preliminary findings on the impact of genome editing across different areas of biological research and applications, and the range of questions to which this gives rise.

Read on:

• Genome editing in brief: what, why and how?
• The context of genome editing
• Moral perspectives
• Human health
• Food
• Wildlife and ecosystems
• Other applications: industrial, military and amateur use
• Conclusions

The next stages of this programme of work will focus on examining and addressing the ethical and practical questions arising in two contexts where genome editing may have a significant impact: firstly, the avoidance of genetic disease and, secondly, livestock farming. Reports on each of these two areas, with recommendations for policy and practice, will be published in 2017.

The full resource can be downloaded here.

Should you edit your children’s genes?

Erika Check Hayden
Nature
Originally posted 23 February 2016

Here is an excerpt:

But emerging technologies are already testing the margins of what people deem acceptable. Parents today have unprecedented control over what they pass on to their children: they can use prenatal genetic screening to check for conditions such as Down’s syndrome, and choose whether or not to carry a fetus to term. Preimplantation genetic diagnosis allows couples undergoing in vitro fertilization to select embryos that do not have certain disease-causing mutations. Even altering the heritable genome — as might be done if CRISPR were used to edit embryos — is acceptable to some. Mitochondrial replacement therapy, which replaces a very small number of genes that a mother passes on with those from a donor, was approved last year in the United Kingdom for people who are at risk of certain genetic disorders.

Many safety, technical and legal barriers still stand in the way of editing DNA in human embryos. But some scientists and ethicists say that it is important to think through the implications of embryo editing now — before these practical hurdles are overcome. What sort of world would these procedures create for those currently living with disease and for future generations?

The article is here.

Scientists get 'gene editing' go-ahead

By James Gallagher
Health editor, BBC News website
Originally published February 1, 2016

UK scientists have been given the go-ahead by the fertility regulator to genetically modify human embryos.

The research will take place at the Francis Crick Institute in London and aims to provide a deeper understanding of the earliest moments of human life.

The experiments will take place in the first seven days after fertilisation and could explain what goes wrong in miscarriage.

It will be illegal for the scientists to implant the embryos into a woman.

Gene editing is the manipulation of our DNA - the blueprint of life.

In a world-first last year, scientists in China announced that they had carried out gene editing in human embryos to correct a gene that causes a blood disorder.

The field is attracting controversy, with some saying that altering the DNA of an embryo is a step too far and opens the door to designer babies.

The entire article is here.

Where to Draw the Line on Gene-Editing Technology

New techniques that could make germline genetic engineering unprecedentedly easy are forcing policymakers to confront the ethical implications of moving forward

By Jonathan D. Moreno
Scientific American
November 30, 2015

The biologists have done it again. Not so long ago it was cloning and embryonic stem cells that challenged moral imagination. These days all eyes are on a powerful new technique for engineering or “editing” DNA. Relatively easy to learn and to use, CRISPR has forced scientists, ethicists and policymakers to reconsider one of the few seeming red lines in experimental biology: the difference between genetically modifying an individual’s somatic cells and engineering the germline that will be transmitted to future generations. Instead of genetic engineering for one person why not eliminate that disease trait from all of her or his descendants?

This week, the U.S. National Academy of Sciences, the Chinese Academy of Sciences, and the U.K. Royal Society are trying to find ways to redraw that red line. And redraw it in a way that allows the technology to help and not to hurt humanity. Perhaps the hardest but most critical part of the ethical challenge: doing that in a way that doesn’t go down a dark path of “improvements” to the human race.

The article is here.