̽��ֱ�� of Cambridge - gene editing

̽��ֱ��lab making food healthier and medicine cheaper

lkm37 — Mon, 16 Dec 2024 10:05:48 +0000

Dr Nicola Patron is cultivating a new kind of biotechnology, where we can read nature’s blueprints and direct its energy to more potent ends.

Study in mice shows potential for gene-editing to tackle mitochondrial disorders

cjb250 — Tue, 08 Feb 2022 10:00:16 +0000

Our cells contain mitochondria, which provide the energy for our cells to function. Each of these mitochondria contains a tiny amount of mitochondrial DNA. Mitochondrial DNA makes up only 0.1% of the overall human genome and is passed down exclusively from mother to child.

Faults in our mitochondrial DNA can affect how well the mitochondria operate, leading to mitochondrial diseases, serious and often fatal conditions that affect around 1 in 5,000 people. ̽��ֱ��diseases are incurable and largely untreatable.

There are typically around 1,000 copies of mitochondrial DNA in each cell, and the percentage of these that are damaged, or mutated, will determine whether a person will suffer from mitochondrial disease or not. Usually, more than 60% of the mitochondria in a cell need to be faulty for the disease to emerge, and the more defective mitochondria a person has, the more severe their disease will be. If the percentage of defective DNA could be reduced, the disease could potentially be treated.

A cell that contains a mixture of healthy and faulty mitochondrial DNA is described as ‘heteroplasmic’. If a cell contains no healthy mitochondrial DNA, it is ‘homoplasmic’.

In 2018, a team from the MRC Mitochondrial Biology Unit at the ̽��ֱ�� of Cambridge applied an experimental gene therapy treatment in mice and were able to successfully target and eliminate the damaged mitochondrial DNA in heteroplasmic cells, allowing mitochondria with healthy DNA to take their place.

“Our earlier approach is very promising and was the first time that anyone had been able to alter mitochondrial DNA in a live animal,” explained Dr Michal Minczuk. “But it would only work in cells with enough healthy mitochondrial DNA to copy themselves and replace the faulty ones that had been removed. It would not work in cells whose entire mitochondria had faulty DNA.”

In their latest advance, published today in Nature Communications, Dr Minczuk and colleagues used a biological tool known as a mitochondrial base editor to edit the mitochondrial DNA of live mice. ̽��ֱ��treatment is delivered into the bloodstream of the mouse using a modified virus, which is then taken up by its cells. ̽��ֱ��tool looks for a unique sequence of base pairs – combinations of the A, C, G and T molecules that make up DNA. It then changes the DNA base – in this case, changing a C to a T. This would, in principle, enable the tool to correct certain ‘spelling mistakes’ that cause the mitochondria to malfunction.

There are currently no suitable mouse models of mitochondrial DNA diseases, so the researchers used healthy mice to test the mitochondrial base editors. However, it shows that it is possible to edit mitochondrial DNA genes in a live animal.

Pedro Silva-Pinheiro, a postdoctoral researcher in Dr Minczuk’s lab and first author of the study, said: “This is the first time that anyone has been able to change DNA base pairs in mitochondria in a live animal. It shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly.”

An approach pioneered in the UK known as mitochondrial replacement therapy – sometimes referred to as ‘three-person IVF’ – allows a mother’s defective mitochondria to be replaced with those from a healthy donor. However, this technique is complex, and even standard IVF is successful in fewer than one in three cycles.

Dr Minczuk added: “There’s clearly a long way to go before our work could lead to a treatment for mitochondrial diseases. But it shows that there is the potential for a future treatment that removes the complexity of mitochondrial replacement therapy and would allow for defective mitochondria to be repaired in children and adults.”

̽��ֱ��research was funded by the Medical Research Council UK, the Champ Foundation and the Lily Foundation.

Reference
Silva-Pinheiro, S et al. In vivo mitochondrial base editing via adenoassociated viral delivery to mouse post-mitotic tissue. Nature Comms; 8 Feb 2022; DOI: 10.1038/s41467-022-28358-w

Defective mitochondria – the ‘batteries’ that power the cells of our bodies – could in future be repaired using gene-editing techniques. Scientists at the ̽��ֱ�� of Cambridge have shown that it is possible to modify the mitochondrial genome in live mice, paving the way for new treatments for incurable mitochondrial disorders.

[This] shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly

Pedro Silva-Pinheiro

wir0man/Getty Images

Mitochondria - 3D illustration

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Mitochondrial diseases could be treated with gene therapy, study suggests

sc604 — Mon, 24 Sep 2018 15:00:00 +0000

̽��ֱ��researchers, led by the ̽��ֱ�� of Cambridge, applied an experimental gene therapy treatment in mice and were able to successfully target and eliminate the damaged DNA in mitochondria which causes the devastating conditions.

Their results, published in the journal Nature Medicine, could provide a practical route to treating patients with these diseases and may provide a future alternative to mitochondrial replacement therapy, or ‘three-parent IVF’. This is the first time programmable genome engineering tools have been used inside a living animal, resulting in such significant modification of mitochondrial DNA.

Mitochondria are the powerhouses inside our cells, producing energy and carrying their own DNA. They are inherited from a person’s mother via the egg, but if they are damaged, it can result in a serious mitochondrial disease. For example, MELAS Syndrome is a severe multi-system disorder causing progressive loss of mental and movement abilities, which usually becomes apparent in early childhood.

There are typically about 1000 copies of mitochondrial DNA per cell, and the percentage of these that are damaged, or mutated, will determine whether a person will suffer from mitochondrial disease or not. Usually, more than 60% of the mitochondrial DNA molecules in a cell need to be mutated for the disease to emerge, and the more mutated mitochondrial DNA a person has, the more severe their disease will be. Conversely, if the percentage of mutated DNA can be reduced, the disease could potentially be treated.

Mitochondrial diseases are currently incurable, although a new IVF technique of mitochondrial transfer gives families affected by mitochondrial disease the chance of having healthy children – removing affected mitochondria from an egg or embryo and replacing them with healthy ones from a donor.

“Mitochondrial replacement therapy is a promising approach to prevent transmission of mitochondrial diseases, however, as the vast majority of mitochondrial diseases have no family history, this approach might not actually reduce the proportion of mitochondrial disease in the population,” said Dr Payam Gammage, a postdoctoral researcher in the MRC Mitochondrial Biology Unit, and the paper’s first author.

“One idea for treating these devastating diseases is to reduce the amount of mutated mitochondrial DNA by selectively destroying the mutated DNA, and allowing healthy DNA to take its place,” said Dr Michal Minczuk, also from the Medical Research Council (MRC) Mitochondrial Biology Unit, and the study’s senior author.

To test an experimental gene therapy treatment, which has so far only been tested in human cells grown in petri dishes in a lab, the researchers used a mouse model of mitochondrial disease that has the same mutation as some human patients.

̽��ֱ��gene therapy treatment, known as the mitochondrially targeted zinc finger-nuclease, or mtZFN, recognises and then eliminates the mutant mitochondrial DNA, based on the DNA sequence differences between healthy and mutant mitochondrial DNA. As cells generally maintain a stable number of mitochondrial DNA copies, the mutated copies that are eliminated are replaced with healthy copies, leading to a decrease in the mitochondrial mutation burden that results in improved mitochondrial function.

̽��ֱ��treatment was delivered into the bloodstream of the mouse using a modified virus, which is then mostly taken up by heart cells. ̽��ֱ��researchers found that the treatment specifically eliminates the mutated mitochondrial DNA, and resulted in measures of heart metabolism improving.

Following on from these results, the researchers hope to take this gene therapy approach through clinical trials, in the hope of producing an effective treatment for mitochondrial diseases.

This work was supported by the Medical Research Council and was performed in collaboration with Sangamo Therapeutics and the Max Planck Institute for Biology of Ageing in Cologne.

Reference:
Payam A. Gammage et al. ‘Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.’ Nature Medicine (2018). DOI: 10.1038/s41591-018-0165-9.

Researchers have developed a genome-editing tool for the potential treatment of mitochondrial diseases: serious and often fatal conditions which affect 1 in 5,000 people.

One idea for treating these devastating diseases is to reduce the amount of mutated mitochondrial DNA by selectively destroying the mutated DNA, and allowing healthy DNA to take its place.

Michal Minczuk

NICHD/U

Mitochondria

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Genome-editing tool could increase cancer risk in cells, say researchers

cjb250 — Mon, 11 Jun 2018 15:00:48 +0000

̽��ֱ��team, led by Professor Jussi Taipale, now at the Department of Biochemistry, Cambridge, found that CRISPR-Cas9 triggers a mechanism designed to protect cells from DNA damage, making gene editing more difficult. Cells which lack this mechanism are easier to edit than normal cells. This can lead to a situation where genome-edited cell populations have increased numbers of cells in which an important mechanism protecting cells against DNA damage is missing.

Discovered in bacteria, the CRISPR-Cas9 system is part of the armoury that bacteria use to protect themselves from the harmful effects of viruses. Today it is being co-opted by scientists worldwide as a way of removing and replacing gene defects.

One part of the CRISPR-Cas9 system acts like a GPS locator that can be programmed to go to an exact place in the genome. ̽��ֱ��other part – the ‘molecular scissors’ – cuts both strands of the faulty DNA so that it can be replaced with DNA that does not have the defect.

However, in a study published today in the journal Nature Medicine, researchers found unexpected consequences from using CRISPR-Cas9.

“We managed to edit cancer cells easily, but when we tried to edit normal, healthy cells, very little happened,” explains Dr Emma Haapaniemi from the Karolinska Institutet, Sweden, the study’s first author.

“When we looked at this further, we found that cutting the genome with CRISPR-Cas9 induced the activation of a protein known as p53, which acts like a cell’s alarm system, signalling that DNA is damaged, and opens the cellular ‘first aid kit’ that repairs damage to the DNA. ̽��ֱ��triggering of this system makes editing much more difficult.”

In fact, this process went further, leading to the strong selection of cells that lacked the p53 pathway. Absence of p53 in cells makes them more likely to become tumorous as damage can no longer be corrected. Around a half of all tumour cells are missing this pathway.

“CRISPR-Cas9 is a very promising biological tool, both for research purposes and for potential life-saving medical treatments, and so has understandably led to great excitement within the scientific community,” says Professor Taipale, who led the work while at the Karolinska Institutet.

“We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns. Like with any medical treatment, there are always side effects or potential harm and this should be balanced against the benefits of the treatment.”

̽��ֱ��team found that by decreasing activity of p53 in a cell, they could more efficiently edit healthy cells. While this might also decrease the risk of selecting for p53-deficient cells, it could leave cells temporarily vulnerable to mutations that cause cancer.

Professor Taipale says that once they better understand how the DNA response is triggered by the cut, it may be possible to prevent this mechanism kicking in, reducing the selective advantage of cells deficient in p53.

“Although we don’t yet understand the mechanisms behind the activation of p53, we believe that researchers need to be aware of the potential risks when developing new treatments,” he adds. “This is why we decided to publish our findings as soon as we discovered that cells edited with CRISPR-Cas9 can go on to become cancerous.”

̽��ֱ��research was supported by the Knut and Alice Wallenberg Foundation, Cancerfonden, Barncancerfonden and the Academy of Finland.

A second team in Novartis Research Institute in Boston, MA, has independently obtained similar results. They are also published today in the same journal.

Reference
Haapaniemi, E et al. CRISPR/Cas9-genome editing induces a p53-mediated DNA damage response. Nature Medicine; 11 June 2018; DOI: 10.1038/s41591-018-0049-z

More research needs to be done to understand whether CRISPR-Cas9 – molecular ‘scissors’ that make gene editing a possibility – may inadvertently increase cancer risk in cells, according to researchers from the ̽��ֱ�� of Cambridge and the Karolinska Institutet.

We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns

Jussi Taipale

ulleo

Scissors cut metal

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Synthetic organs, nanobots and DNA ‘scissors’: the future of medicine

lw355 — Thu, 12 Oct 2017 08:00:43 +0000

In a new film to coincide with the recent launch of the Cambridge Academy of Therapeutic Sciences, researchers discuss some of the most exciting developments in medical research and set out their vision for the next 50 years.

Professor Jeremy Baumberg from the NanoPhotonics Centre discusses a future in which diagnoses do not have to rely on asking a patient how they are feeling, but rather are carried out by nanomachines that patrol our bodies, looking for and repairing problems. Professor Michelle Oyen from the Department of Engineering talks about using artificial scaffolds to create ‘off-the-shelf’ replacement organs that could help solve the shortage of donated organs. Dr Sanjay Sinha from the Wellcome Trust-MRC Stem Cell Institute sees us using stem cell ‘patches’ to repair damaged hearts and return their function back to normal.

Dr Alasdair Russell from the Cancer Research UK Cambridge Institute describes how recent breakthroughs in the use of CRISPR-Cas9 – a DNA editing tool – will enable us to snip out and replace defective regions of the genome, curing diseases in individual patients; and lawyer Dr Kathy Liddell, from the Cambridge Centre for Law, Medicine and Life Sciences, highlights how research around law and ethics will help to make gene editing safe.

Professor Gillian Griffiths, Director of the Cambridge Institute for Medical Research, envisages us weaponising ‘killer T cells’ – important immune system warriors – to hunt down and destroy even the most evasive of cancer cells.

All of these developments will help transform the field of medicine, says Professor Chris Lowe, Director of the Cambridge Academy of Therapeutic Sciences, who sees this as an exciting time for medicine. New developments have the potential to transform healthcare “right the way from how you handle the patient to actually delivering the final therapeutic product - and that’s the exciting thing”.

Read more about research on future therapeutics in Research Horizons magazine.

Nanobots that patrol our bodies, killer immune cells hunting and destroying cancer cells, biological scissors that cut out defective genes: these are just some of technologies that Cambridge researchers are developing which are set to revolutionise medicine in the future.

̽��ֱ��Future of Medicine

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Genome editing reveals role of gene important for human embryo development

sc604 — Wed, 20 Sep 2017 17:00:00 +0000

̽��ֱ��team used genome editing techniques to stop a key gene from producing a protein called OCT4, which normally becomes active in the first few days of human embryo development. After the egg is fertilised, it divides until at about 7 days it forms a ball of around 200 cells called the ‘blastocyst’. ̽��ֱ��study found that human embryos need OCT4 to correctly form a blastocyst.

“We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role” says Dr Norah Fogarty from the Francis Crick Institute, first author of the study. “Other research methods, including studies in mice, suggested a later and more focussed role for OCT4, so our results highlight the need for human embryo research.”

Dr Kathy Niakan from the Francis Crick Institute, who led the research adds, “One way to find out what a gene does in the developing embryo is to see what happens when it isn’t working. Now we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes. If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure. It will take many years to achieve such an understanding, our study is just the first step.”

̽��ֱ��research was published in Nature and led by scientists at the Francis Crick Institute, in collaboration with colleagues at Cambridge ̽��ֱ��, Oxford ̽��ֱ��, the Wellcome Trust Sanger Institute, Seoul National ̽��ֱ�� and Bourn Hall Clinic. It was chiefly funded by the UK Medical Research Council, Wellcome and Cancer Research.

̽��ֱ��team spent over a year optimising their techniques using mouse embryos and human embryonic stem cells before starting work on human embryos. To inactivate OCT4, they used an editing technique called CRISPR/Cas9 to change the DNA of 41 human embryos. After seven days, embryo development was stopped and the embryos were analysed.

̽��ֱ��embryos used in the study were donated by couples who had undergone IVF treatment, with frozen embryos remaining in storage; the majority were donated by couples who had completed their family, and wanted their surplus embryos to be used for research. ̽��ֱ��study was done under a research licence and strict regulatory oversight from the Human Fertilisation and Embryology Authority (HFEA), the UK Government's independent regulator overseeing infertility treatment and research.

As well as human embryo development, OCT4 is thought to be important in stem cell biology. ‘Pluripotent’ stem cells can become any other type of cell, and they can be derived from embryos or created from adult cells such as skin cells. Human embryonic stem cells are taken from a part of the developing embryo that has high levels of OCT4.

“We have the technology to create and use pluripotent stem cells, which is undoubtedly a fantastic achievement, but we still don’t understand exactly how these cells work,” explains Dr James Turner, co-author of the study from the Francis Crick Institute. “Learning more about how different genes cause cells to become and remain pluripotent will help us to produce and use stem cells more reliably.”

Sir Paul Nurse, Director of the Francis Crick Institute, says: “This is exciting and important research. ̽��ֱ��study has been carried out with full regulatory oversight and offers new knowledge of the biological processes at work in the first five or six days of a human embryo’s healthy development. Kathy Niakan and colleagues are providing new understanding of the genes responsible for a crucial change when groups of cells in the very early embryo first become organised and set on different paths of development. ̽��ֱ��processes at work in these embryonic cells will be of interest in many areas of stem cell biology and medicine.”

Dr. Kay Elder, study co-author from the Bourn Hall Clinic, says: "Successful IVF treatment is crucially dependent on culture systems that provide an optimal environment for healthy embryo development. Many embryos arrest in culture, or fail to continue developing after implantation; this research will significantly help treatment for infertile couples, by helping us to identify the factors that are essential for ensuring that human embryos can develop into healthy babies.”

Dr Ludovic Vallier, co-author on the study from the Wellcome Trust Sanger Institute and the Wellcome - MRC Cambridge Stem Cell Institute, said: “This study represents an important step in understanding human embryonic development. ̽��ֱ��acquisition of this knowledge will be essential to develop new treatments against developmental disorders and could also help understand adult diseases such as diabetes that may originate during the early stage of life. Thus, this research will open new fields of opportunity for basic and translational applications.”

Reference:
Norah M.E. Fogarty et al. 'Genome editing of OCT4 reveals distinct mechanisms of lineage specification in human and mouse embryos.' Nature (2017). DOI: 10.1038/nature24033.

Adapted from a Francis Crick Institute press release.

Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human embryos, which could help scientists to better understand the biology of our early development.

This knowledge will be essential to develop new treatments against developmental disorders and could also help understand adult diseases such as diabetes that may originate during the early stage of life.

Ludovic Vallier

Dr Kathy Niakan/Nature

Day 2 embryo

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Snip, snip, cure: correcting defects in the genetic blueprint

lw355 — Fri, 14 Jul 2017 08:01:02 +0000

Dr James Thaventhiran points to a diagram of a 14-year-old boy’s family tree. Some of the symbols are shaded black.

“These family members have a very severe form of immunodeficiency. ̽��ֱ��children get infections and chest problems, the adults have bowel problems, and the father died from cancer during the study. ̽��ֱ��boy himself had a donor bone marrow transplant when he was a teenager, but he remains very unwell, with limited treatment options.”

To understand the cause of the immunodeficiency, Thaventhiran, a clinical immunologist in Cambridge’s Department of Medicine, has been working with colleagues at the Great Northern Children’s Hospital in Newcastle, where the family is being treated.

Theirs is a rare disease, which means the condition affects fewer than 1 in 2,000 people. Most rare diseases are caused by a defect in the genetic blueprint that carries the instruction manual for life. Sometimes the mistake can be as small as a single letter in the three billion letters that make up the genome, yet it can have devastating consequences.

When Thaventhiran and colleagues at the National Institute for Health Research (NIHR) BioResource in Cambridge carried out whole genome sequencing on the boy’s DNA, they discovered a defect that could explain the immunodeficiency. “We believe that just one wrong letter causes a malfunction in an immune cell called a dendritic cell, which is needed to detect infections and cancerous cells.”

Now, hope for an eventual cure for family members affected by the faulty gene is taking shape in the form of ‘molecular scissors’ called CRISPR-Cas9. Discovered in bacteria, the CRISPR-Cas9 system is part of the armoury that bacteria use to protect themselves from the harmful effects of viruses. Today it is being co-opted by scientists worldwide as a way of removing and replacing gene defects.

One part of the CRISPR-Cas9 system acts like a GPS locator that can be programmed to go to an exact place in the genome. ̽��ֱ��other part – the ‘molecular scissors’ – cuts both strands of the faulty DNA and replaces it with DNA that doesn’t have the defect.

“It’s like rewriting DNA with precision,” explains Dr Alasdair Russell. “Unlike other forms of gene therapy, in which cells are given a new working gene but without being able to direct where it ends up in the genome, this technology changes just the faulty gene. It’s precise and it’s ‘scarless’ in that no evidence of the therapy is left within the repaired genome.”

Russell heads up a specialised team in the Cancer Research UK Cambridge Institute to provide a centralised hub for state-of-the-art genome-editing technologies.

“By concentrating skills in one area, it means scientists in different labs don’t reinvent the wheel each time and can keep pace with the field,” he explains. “At full capacity, we aim to be capable of running up to 30 gene-editing projects in parallel.

“What I find amazing about the technology is that it’s tearing down traditional barriers between different disciplines, allowing us to collaborate with clinicians, synthetic biologists, physicists, engineers, computational analysts and industry, on a global scale. ̽��ֱ��technology gives you the opportunity to innovate, rather than imitate. I tell my wife I sometimes feel like Q in James Bond and she laughs.”

Russell’s team is using the technology both to understand disease and to treat it. Together with Cambridge spin-out DefiniGEN, they are rewriting the DNA of a very special type of cell called an induced pluripotent stem cell (iPSC). These are cells that are taken from the skin of a patient and ‘reprogrammed’ to act like one of the body’s stem cells, which have the capacity to develop into almost any other cell of the body.

In this case, they are turning the boy’s skin cells into iPSCs, using CRISPR-Cas9 to correct the defect, and then allowing these corrected cells to develop into the cell type that is affected by the disease – the dendritic cell. “It’s a patient-specific model of the cure in a Petri dish,” says Russell.

̽��ֱ��boy’s family members are among a handful of patients worldwide who are reported to have the same condition and among around 3,500 in the UK who have similar types of immunodeficiency caused by other gene defects. With such a rare group of diseases, explains Thaventhiran, it’s important to locate other patients to increase the chance of understanding what happens and how to treat it.

He and Professor Ken Smith in the Department of Medicine lead a programme to find, research and provide diagnostic services to these patients. So far, 2,000 patients (around 60% of the total affected in the UK) have been recruited and sequenced by the NIHR Bioresource, making it the largest worldwide cohort of patients with primary immunodeficiency."

“We’ve now made 12 iPSC lines from different patients with immunodeficiency,” adds Thaventhiran, who has started a programme for gene editing all of the lines. “This means that for the first time we’ll be able to investigate whether correcting the mutation corrects the defect – it’ll open up new avenues of research into the mechanisms underlying these diseases.”

But it’s the possibility of using the gene-edited cells to cure patients that excites Thaventhiran and Russell. They explain that one option might be to give a patient repeated treatments of their own gene-edited iPSCs. Another would be to take the patient’s blood stem cells, edit them and then return them to the patient.

̽��ֱ��researchers are quick to point out that although the technologies are converging on this possibility of truly personalised medicine, there are still many issues to consider in the fields of ethics, regulation and law.

Dr Kathy Liddell, who leads the Cambridge Centre for Law, Medicine and Life Sciences, agrees: “It’s easy to see the appeal of using gene editing to help patients with serious illnesses. However, new techniques could be used for many purposes, some of which are contentious. For example, the same technique that edits a disease in a child could be applied to an embryo to stop a disease being inherited, or to ‘design’ babies. This raises concerns about eugenics.

“ ̽��ֱ��challenge is to find systems of governance that facilitate important purposes, while limiting, and preferably preventing, unethical purposes. It’s actually very difficult. Rules not only have to be designed, but implemented and enforced. Meanwhile, powerful social drivers push hard against ethical boundaries, and scientific information and ideas travel easily – often too easily – across national borders to unregulated states.”

A further challenge is the business case for carrying out these types of treatments, which are potentially curative but are costly and benefit few patients. One reason why rare diseases are also known as orphan diseases is because in the past they have rarely been adopted by drug companies.

Liddell adds: “CRISPR-Cas9 patent wars are just warming up, demonstrating some of the economic issues at stake. Two US institutions are vigorously prosecuting their own patents, and trying to overturn the others. There will also be cross-licensing battles to follow.”

“ ̽��ֱ��obvious place to start is by correcting diseases caused by just one gene; however, the technology allows us to scale up to several genes, making it something that could benefit many, many different diseases,” adds Russell. “At the moment, the field as a whole is focused on ensuring the technology is safe before it moves into the clinic. But the advantage of it being cheap, precise and scalable should make CRISPR attractive to industry.”

In ten years or so, speculates Russell, we might see bedside ‘CRISPR on a chip’ devices that screen for mutations and ‘edit on the fly’. “I’m really excited by the frontierness of it all,” says Russell. “We feel that we’re right on the precipice of a new personalised medical future.”

Gene editing using ‘molecular scissors’ that snip out and replace faulty DNA could provide an almost unimaginable future for some patients: a complete cure. Cambridge researchers are working towards making the technology cheap and safe, as well as examining the ethical and legal issues surrounding one of the most exciting medical advances of recent times.

I’m really excited by the frontierness of it all. We feel that we’re right on the precipice of a new personalised medical future.

Alasdair Russell

̽��ֱ��District

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