The Russian community of geneticists, clinicians and bioethicists have reached a consensus on the use of genome-editing technologies on human embryos and germ cells for clinical purposes. They consider that such experiments are premature at this point. Their view aligns with the position of the Russian ministry of health and sets the social context for further discussion of the technology.
Russian biologist Denis Rebrikov has started gene editing in eggs donated by women who can hear to learn how to allow some deaf couples to give birth to children without the genetic mutation that impairs hearing. The news, detailed in an e-mail he sent to Nature on 17 October, is the latest in a saga that kicked off in June, when Rebrikov told Nature of his controversial intention to create gene-edited babies resistant to HIV using the popular CRISPR tool.Rebrikov’s latest e-mail follows a September report in Russian magazine N+1 that one deaf couple had started procedures to procure eggs that would be used to create a gene-edited baby — but the eggs that Rebrikov has edited are from women without the genetic mutation that can impair hearing. He says the goal of the experiments is to better understand potentially harmful ‘off-target’ mutations, which are a known challenge of using CRISR–Cas9 to edit embryos.
The US Food and Drug Administration (FDA) has approved a chicken that has been genetically engineered to produce a drug in its eggs.
The drug, Kanuma (sebelipase alfa), is a recombinant human enzyme marketed by Alexion Pharmaceuticals. It replaces a faulty enzyme in people with a rare, inherited condition that prevents the body from breaking down fatty molecules in cells.
Following its approval by the FDA on 8 December, Kanuma joins a small group of ‘farmaceuticals’ on the US market. In 2009, the agencyapproved genetically modified goats that produce an anticoagulant called ATryn (antithrombin) in their milk. And last year, the FDA authorized a drug for treating hereditary angioedema that is produced by transgenic rabbits.
The FDA’s latest decision “shows that the ATryn goats weren’t just a one-off”, says Jay Cormier, a lawyer at Hyman, Phelps and McNamara in Washington DC and a former scientific reviewer for the FDA. “The process can function for more than just one particular unique case.”
The agency moved quickly to consider Kanuma, giving it a priority review, orphan-drug status and a breakthrough-therapy designation. The disease that it is designed to treat, lysosomal acid lipase deficiency, causes fat to accumulate in the liver, spleen and vasculature. A form of the disease that strikes infants is quickly fatal. A second form that affects older patients causes liver enlargement, fibrosis and cirrhosis, as well as cardiovascular disease.
“Before we had this drug, we didn’t have any treatment for the patients that really addressed the underlying biochemical defect in the disorder,” says Barbara Burton, a paediatrician with the Northwestern University Feinberg School of Medicine in Chicago, Illinois. Clinicians could only provide nutrition and supportive care to infants, says Burton, who worked with Alexion to conduct the clinical trials. Older patients are treated with statins—which do not address the fatty build-up in the liver.
Stepping toward therapeutic CRISPR
Authors:
Gagnon et al
Abstract:
Most new technologies for manipulating gene expression in mammalian cells are accepted at a relatively slow pace. Occasionally, however, a new technology is so robust and fills such a critical niche that its adoption is widespread and rapid. Fifteen years ago, duplex RNAs were such a technology. RNA interference (RNAi) in mammalian cells was first demonstrated in 2001 (1) and within 2 y RNAi was a commonly used tool throughout industry and academia. RNAi is making its way into clinical trials as a potential therapeutic as challenges in delivery to relevant tissues begin to be overcome (2–4).
Gene editing has received a lot of press recently, thanks to a slew of recent advancements that allow scientists to do ever more with plant and animal genomes. Techniques, such as CRISPR-Cas9, are opening the doors to novel genetically modified crops (GMOs), stem cell research, synthetic biology and even experiments with human embryos.
However, with this explosion of research has come intense scrutiny. Modifying DNA, the blueprint of an organism, carries with it powerful implications and unknown risks. Just last week, an international summit on human gene editing was convened in Washington D.C. to discuss ethical guidelines for future gene editing research, among other agenda items. One of the biggest concerns about genetic modification is the potential for engineered microbes with altered DNA to escape the lab and wreak havoc on an unprepared world. Like Frankenstein’s monster, the fear is that these organisms may prove harmful to humans and difficult to stop. Fortunately, scientists have been working hard to ensure this nightmare scenario doesn’t occur.
Don't look now, but the future just pulled into town.
Hundreds of scientists, policymakers and the president's science adviser have gathered Tuesday in Washington for what will be a three-day summit on genetic engineering, with a focus on a new, relatively simple technique for manipulating genes. It's fast and flexible, and just about anybody with some lab equipment and a little know-how can potentially alter the human species. The technique is called CRISPR-Cas9, or simply CRISPR, and more generically referred to as "gene editing."
The summit kicked off early Tuesday morning at the headquarters of the National Academy of Sciences, which is one of the sponsors, along with the National Academy of Medicine, the Royal Academy (Britain), and the Chinese Academy of Sciences. The Chinese scientists have been aggressive in using CRISPR, and one team made news this year when it reported results from experiments on nonviable human embryos.
“The overriding question is when, if ever, we will want to use gene editing to change human inheritance," summit chair David Baltimore of Caltech said in his introductory remarks.
A twist on a revolutionary gene-editing technique may make it possible to modify plant genomes while sidestepping national biosafety regulations, South Korean researchers say.
Plant scientists have been quick to experiment with the popular CRISPR/Cas9 technique, which uses an enzyme called Cas9, guided by two RNA strands, to precisely cut segments of DNA in a genome. By disabling specific genes in wheat and rice, for example, researchers hope to make disease-resistant strains of the crops.
But the process can introduce bits of foreign DNA into plant genomes. And some jurisdictions, such as the European Union, could decide to classify such plants as genetically modified organisms (GMOs) — making their acceptance by regulatory bodies contentious, says geneticist Jin-Soo Kim of Seoul National University.
Kim and his team tweaked the technique so that it can delete specific plant genes without introducing foreign DNA, creating plants that he and his colleagues think “might be exempt from current GMO regulations”.
They are meeting in China; they are meeting in the United Kingdom; and they met in the United States last week. Around the world, scientists are gathering to discuss the promise and perils of editing the genome of a human embryo. Should it be allowed — and if so, under what circumstances?
The meetings have been prompted by an explosion of interest in the powerful technology known as CRISPR/Cas9, which has brought unprecedented ease and precision to genetic engineering. This tool, and others like it, could be used to manipulate the DNA of embryos in a dish to learn about the earliest stages of human development. In theory, genome editing could also be used to 'fix' the mutations responsible for heritable human diseases. If done in embryos, this could prevent such diseases from being passed on.
The prospects have prompted widespread concern and discussion among scientists, ethicists and patients. Fears loom that if genome editing becomes acceptable in the clinic to stave off disease, it will inevitably come to be used to introduce, enhance or eliminate traits for non-medical reasons. Ethicists are concerned that unequal access to such technologies could lead to genetic classism. And targeted changes to a person's genome would be passed on for generations, through the germ line (sperm and eggs), fuelling fears that embryo editing could have lasting, unintended consequences.
The US House of Representatives is wading into the debate over whether human embryos should be modified to introduce heritable changes. Its fiscal year 2016 spending bill for the US Food and Drug Administration (FDA) would prohibit the agency from spending money to evaluate research or clinical applications for such products.
In an unusual twist, the bill—introduced on June 17—would also direct the FDA to create a committee that includes religious experts to review a forthcoming report from the US Institute of Medicine (IOM). The IOM's analysis, which considers the ethics of creating embryos that have three genetic parents, was commissioned by the FDA.
The House legislation comes during a time of intense debate on such matters, sparked by the announcement in April that researchers in China had edited the genomes of human embryos. The US National Institutes of Health (NIH) moved quickly to remind the public that a 1996 law prevents the federal government from funding work that destroys human embryos or creates them for research purposes.
In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted—rumours that sparked a high-profile debate last month about the ethical implications of such work.
In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using 'non-viable' embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.
"I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale," says George Daley, a stem-cell biologist at Harvard Medical School in Boston. "Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes."
Genome engineering technologies have revolutionized genetics, biotechnology, and medical research. We may soon be able to alter not just domesticated species, but entire wild populations and ecosystems. Why, when and how might we use these novel methods to reshape our environment?
The story begins with a new technology that has made the precise editing of genes in many different organisms much easier than ever before. The so-called “CRISPR” system naturally protects bacteria from viruses by storing fragments of viral DNA sequence and cutting any sequences that exactly match the fragment. By changing the fragments and delivering the altered system into other organisms, we can cut any given gene. If we also supply a DNA sequence that the cell can use to repair the damage, it will incorporate this new DNA, precisely editing the genome. When performed in the cells that give rise to eggs or sperm, these changes will be inherited by future generations. Because most altered traits don’t improve and may even decrease the organism’s ability to survive and reproduce, they generally can’t spread through wild populations.
Get ready: The "new genetics" promises to change faulty genes of future generations by introducing new, functioning genes using "designer sperm." A new research report appearing online in The FASEB Journal, shows that introducing new genetic material via a viral vector into the sperm of mice leads to the presence and activity of those genes in the resulting embryos. This new genetic material is actually inherited, present and functioning through three generations of the mice tested. This discovery—if successful in humans—could lead to a new frontier in genetic medicine in which diseases and disorders are effectively cured, and new human attributes, such as organ regeneration, may be possible.
"Transgenic technology is a most important tool for researching all kinds of disease in humans and animals, and for understanding crucial problems in biology," said Anil Chandrashekran, Ph.D., study author from the Department of Veterinary Clinical Sciences at The Royal Veterinary College in North Mimms, United Kingdom.
To achieve these results, Chandrashekran and colleagues used lentiviruses to generate transgenic animals via the male germ line. When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were incubated with mouse spermatozoa, these sperm were highly successful in producing transgenics. Lentivirally-transduced mouse spermatozoa were used in in vitro fertilization studies and when followed by embryo transfer, at least 42 percent of founders were transgenic for GFP. GFP expression was detected in a wide range of murine tissues, including testis and the transgene was stably transmitted to a third generation of transgenic animals.
"Using modified sperm to insert genetic material has the potential to be a major breakthrough not only in future research, but also in human medicine," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "It facilitates the development of transgenic animal models, and may lead to therapeutic benefits for people as well. For years we have chased effective gene therapies and have hit numerous speed bumps and dead ends. If we are able to able to alter sperm to improve the health of future generations, it would completely change our notions of 'preventative medicine.'"
As described in a patent recently granted by the United States Patent Office, consumer genomics company 23andMe has developed a system for helping prospective parents choose the traits of their offspring, from disease risk to hair color. Put another way, it’s a designer baby-making system.link.
The company says it does not intend to use the technology this way. “When we originally introduced the tool and filed the patent there was some thinking the feature could have applications for fertility clinics,” said Catherine Afarian, a 23andMe spokeswoman. “But we’ve never pursued the idea, and have no plans to do so.”
Filed in December 2008, the patent — number 8543339, “Gamete donor selection based on genetic calculations” — sounds like something out of Gattaca, the 1997 movie that came to symbolize tensions between self-determination and biologically ordained fate.
The patent describes a technology that would take a customer’s preferences for a child’s traits, compute the likely genomic outcomes of combinations between a customer’s sperm or egg and other people’s sex cells, and describe which potential reproductive matches would most likely produce the desired baby.
Among the traits listed in the application as examples of possible choice are: height, weight, hair color, risks of colorectal cancer and congenital heart defects, expected life span, expected lifetime health care costs, and athleticism. The company, which has about 400,000 customers, offers genomic analysis of more than 240 traits altogether, from Alzheimer’s disease risk to breast shape and memory. Additional traits from this longer list could presumably be used the same way.
