Category Archives: Transhuman News

April 24, 2017 Credit: Cancer Research UK

It's been a couple of years since the genome editing tool CRISPR first hit the headlines. And talk of its potential to cure all manner of diseases, create superhumans and bring dinosaurs back from the dead has followed.

But among that speculation, one area of medicine has been quick to pick up the technology and is now leading the way in early clinical trials.

In this second post in our series taking a closer look at CRISPR, we explore its potential for new developments in cancer immunotherapy.

Immunotherapy can take a range of forms. Some experimental approaches use viruses that kill cancer cells and alert the immune system to attack. Others involve giving patients drugs that release the 'brakes' on immune cells to target cancer. And some use specially engineered immune cells that when injected into a patient have the potential to hunt out and kill cancer cells.The aim of immunotherapy treatments is to alert the body's immune system to cancer, so that it's better equipped to recognise and fight the disease.

In each of these cases, scientists need to be able to understand and fine-tune the body's complex immune system. And some are turning to CRISPR for help.

Dr Martin Pule, a clinical senior lecturer in haematology at UCL, says that genome editing techniques such as CRISPR have quickly become part of the tool-kit for researchers like him.

"In the past, many of the technical problems around introducing new genes into cells were worked out, but we didn't have an easy way of efficiently and precisely disrupting existing genes," he says. "New genome editing technologies changed all that."

By using CRISPR, scientists are able to tweak specific genes in viruses or the body's own immune cells, and so make them behave differently.

Researchers have been able to do this before using similar techniques, but the excitement around CRISPR is that this can be done much quicker, cheaper and more precisely than ever before.

Out of the lab, into the patient

Genome editing techniques have been used in people to treat cancer and other diseases before.

There was lots of excitement when news broke in 2015 of a 1 year old girl with acute lymphoblastic leukaemia (ALL) being treated with a similar editing technique known as TALENs, after all other treatments had failed.

She received a transplant of cancer-fighting immune T cells from a donor, which had been tweaked in the lab to give them 2 new characteristics.

Normally, the donated cells would see their new environment as foreign and attack the patient's healthy cells, but genes that control this process were turned off. The T cells would also be susceptible to attack from the anti-cancer drugs that the baby was receiving, and so modifications were made to protect them.

She responded well to the treatment, and another infant received a similar therapy.

Following in the footsteps of its cousin TALENs, CRISPR itself has moved on from the lab to clinical trials. Late last year, a Chinese group became the first to use CRISPR-edited cells in humans.

The team took immune cells from a patient with an aggressive lung cancer and edited them in the lab. This editing deactivates a gene that allows tumours to put the 'brakes' on these immune cells, preventing them from attacking cancer cells.

By switching off the gene, which produces a molecule on the cells' surface called PD-1, the full force of the body's immune system is released, helping it clear the tumour. Drugs that target PD-1 are among the much-lauded immunotherapy treatments already showing promise in advanced melanoma and lung cancers. So there's a lot of hope that CRISPR may provide another step forward here too.

10 patients will be involved in the early-stage Chinese trial, and it will look at whether the treatment is safe, rather than testing effectiveness.

The scientists are also hoping to start clinical trials using CRISPR to treat bladder,prostateandkidney cancers. It's also positive news that both blood cancers and solid tumours appear to be responding to various immunotherapy approaches, as different challenges are faced in treating these diseases.

Kickstart the CAR

One clever immunotherapy trick fuses together 2 components of the immune system with different jobs.

Chimeric antigen receptor (CAR) T cells are a mix of an antibody molecule, which can home in on a specific target on tumour cells, fused to a T cell that provides the knock-out blow to the cancer cell.

We've blogged before about how these engineered cells work, and small trials in 2011 caused lots of excitement. But one of the latest updates is that using CRISPR instead of older genome editing techniques might supercharge these CAR T-cells even further.

The older technology is less precise and can result in the genes mistakenly being inserted at random locations in the cell's DNA. The knock-on effect is that the engineered cells' might be less effective or unintended side-effects could be introduced.

But a US-based group found that CRISPR improved the precision with which the modified gene was inserted into T cells. Their research suggests that the cells were then more potent in their fight against leukaemia in mice because they had more stamina. The researchers are now hoping to test these findings in people.

"Cancer cells are relentless in their attempt to evade treatment, so we need CAR T cells that can match and outlast them," Dr Michel Sadelain, the researcher leading the study at Memorial Sloan Kettering Cancer Center, said at the time.

It's findings like these that will hopefully make engineered immune cell treatments better and kinder in the future, though they aren't yet the Holy Grail.

"In one kind of leukaemia called B-ALL, almost 100% of children who received engineered T cells responded, despite having a disease which had become resistant to all standard treatments," says Pule.

This suggests that, in some circumstances, there may not be an upper limit on who may respond to these treatments. But achieving this in other cancers will take further fine-tuning. In other diseases, such as another kind of blood cancer called DLBCL, the response rates are more like 60%.`

"This reflects the fact that a good CAR T cell product is hard to make, or that there are factors inside the tumour making the T cells less effective," Pule adds.

Lots of the progress using CAR T cells has so far been in blood cancers rather than solid tumours, which have even tougher conditions.

Because CRISPR allows scientists to do lots of small-scale tinkering, this is a rapidly developing field and researchers are trying to find solutions.

"Right now a lot of people are asking why there's this response gap between DLBCL and B-ALL. Can we edit something in the CAR T cell, or put something extra in which will increase the response rates?"

One reason might be that the tumour lives in a hostile environment that stops the engineered T-cells' ability to attack the cancer cells. One way around this is to delete the molecules on T cells that coordinate the stop messages from the microenvironment.

"This strategy looks like it might be quite effective and could increase the number of patients who respond," says Pule.

The other side of immunotherapy

Some of the research that's taken place since CRISPR burst onto the scene has also raised more questions than answers. The immune system is a powerful and complicated machine, and we don't yet understand how to control it.

Not all of these treatments have been as successful as hoped. As well as varying response rates, they can also cause serious side effects, including, in rare cases, death.

There have been recent reports of patients with bladder cancer whose tumours increased in size after immunotherapy treatment, although this has caused some debate among researchers. Side effects including extreme fever or organ damage have also been well documented in clinical trials.

In the US, a total of 5 patients died following treatment with an experimental CAR T cell therapy for ALL. The clinical trial was paused after 3 people died, and then stopped after 2 more deaths.

While this is very rare, it's clear that as well as working to make treatments more effective in more people, researchers also need to look at how they can reduce side effects.

Similar problems were seen in the past in the early days of treatments such as combination chemotherapy, before they were refined.

Pule points to how scientists are already using genome editing to increase safety. For example, in many cases, it isn't possible to engineer a patient's own T cells and so cells from a donor are needed.

But this raises some challenges.

"The donor T cells might attack the recipient causing graft-versus-host disease," says Pule. Graft-versus-host disease is a condition where the donor cells see their new environment as foreign and attack it. "If we remove a specific molecule in the donor T cells using gene-editing technology, we can reduce the chance of this happening."

This is how the two infants with ALL were treated.

Where next?

Like many new technologies, CRISPR was greeted with excited fanfare in some parts, and a more cautious realism is now settling in.

It's clear that CRISPR opens up so many doors for immunotherapy and lets researchers go further, more easily than ever before. But as the technology is understood better, its limitations and challenges also come into focus.

The third part of our CRISPR series will take a look at what the future might hold for CRISPR and cancer research.

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CRISPR genome editing and immunotherapy the early adopter - Medical Xpress

THE THEOLOGY CHAPTERS

Scots first chapter deals with four principles with which to read the Bible. As Scot says at the outset Theology which is designed to investigate that nonempirical reality in some ways, can provide a map onto which we can locate science and which can challenge science. (p. 95). Exactly my point. The empirically observable and testable world is not all there is to reality. Scots concern is we will all gain clarity if Christians learn how to speak about Adam and Eve in a context that both affirms conclusions about the genome and challenges some conclusions drawn from the Human Genome Project. (p. 97).

The first of the four principles by which to study the Bible and talk with others about it is respect and respectful discourse for disciplines other than Biblical studies, and in this case science, and particularly genetics. I agree with Scots statement on p. 99 that it is disrespectful to Scripture itself to expect the authors of Gen. 1-11 to be scientists in advance of the scientific era that already understand DNA etc. There is no evidence that they did.

If one takes the related field of cosmology, what we have is the use of phenomenological not scientific language about the relationship of our sun to earth. They talk about the sun rising and setting, which is true from an earthbound observational point of view. Thats how it looks to us. Its not the reality of the situation however. Such observations are not intended to teach us cosmology, merely how things appeared to these ancient people, and indeed, how it appears still today to us. Scot spends considerable time situating Gen. 1-11 in its ANE context in some helpful ways as we shall see. He even recites my favorite dictuma text without a context is just a pretext for whatever you want it to mean.

The second valuable principle is honesty, and again I fully agree. Fundamentalists react to science as if it were a contagious disease, and come up with fear-based theories about both the Bible and science, neither of which are helpful. It results in bad history and bad Bible interpretation and bad science too, the worst of both worlds.

I will certainly never forget the time I hitch-hiked back from the mountains of N.C. in 1969 with two flat landers, who insisted that the moon walk by Neal Armstrong and all those pictures of a beautiful round and revolving earth were a Hollywood stunt. When my friend Doug asked why they thought it was fake the answer was it says in the book of Revelations that the angels will stand on the four corners of the earth. Cant be round if it has four corners. Bless their hearts these folks did not know that apocalyptic literature isnt teaching cosmology, its teaching eschatology, and the whole point was the angels would round up people from all points on the compass, not that the earth was flat! Sometimes invincible ignorance is impossible to dialogue with.

See original here:
Adam and Genome Part Eight - Patheos (blog)

I must admit, I am less willing to critique all the intelligent design folks the way Venema does at the end of his last chapter. I think there is far more to some of their arguments than some would allow. Some of these folks are actual scientists who are also people of faith and are struggling to make sense of both the Bible and evolution. Good for them. We need more, not less efforts to bring the two disciplines together for dialogue, and that does not include and assumption the science and its theories should go unchallenged, and that Bible interpretation should simply adapt to the brave new world of genetic truth.

The third principle Scot mentions is sensitivity to students of science, and again, I totally agree. I do not know if Scots claim on p. 104 that the number 1 reason kids leave the faith is because of questions about science, is true, but certainly some do. In light of the second half of this book, one should be equally concerned about students leaving the faith because someone told them that Adam and Eve did not exist as historical persons. The undercutting of the historical foundations of the Bible can be equally damaging to someones faith.

Scots fourth principle is also a useful one Scot says prima Scriptura is better than sola Scriptura, and I agree if we are talking about knowledge or truth in general. If we are talking salvation, sola Scriptura is closer to the truth.

Read more from the original source:
Adam and the Genome Part Nine - Patheos (blog)

Looping the genome: How cohesin does the trick Science Daily Defined genome-sequences that were previously located far apart are now next to each other and can interact to regulate gene expression. In Nature online this week, IMP-researchers publish data that support the existence of such a mechanism. First ...

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Looping the genome: How cohesin does the trick - Science Daily

NEW YORK, April 24, 2017 /PRNewswire/ --Dante Labs announced today the offer of whole genome sequencing (WGS) and interpretation at only EUR 850 (ca. $900). While American individuals have been able to access WGS at $1,000, this innovation marks the first time Europeans can access WGS below EUR 1,000.

The sequencing includes bioinformatics analysis and interpretation, which are crucial to leveraging genetic information to make informed decisions about disease monitoring, prevention, nutrition, exercise, health monitoring and more.

WGS is run at 30X coverage, which makes the achievement even more impressive.

Dante Labs has chosen a select list of partners to develop DNA sequencing services that are "accessible to everyone ... By leveraging only the world's best genetic technologies, we ensure that our customers have access to the best in the world of genetics", says Dante Labs co-founder Andrea Riposati. "Genetics has seen tremendous developments in the last decade. Just think that the first whole genome sequencing cost north of $2.4 billion. For too long, only [a] few people could benefit from the impact of genetic research. It's healthcare, so I say it is important [that] everyone benefits from it. The key to empower[ing] everyone with high-quality, advanced genetics is to decrease the price. By integrating in the value chain, removing unnecessary intermediaries, developing synergies with strategic partners and leveraging economies of scale, we are able to offer whole genome sequencing at only EUR 850".

Dante Labs offers a suite of direct-to-consumer DNA tests, including BRCA1 and BRCA2 sequencing, whole exome sequencing and common hereditary cancer testing.

Media Contact: FrancescoPennelli Phone: +39.320.603.0072 Email: francesco@dantelabs.com

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SOURCE Dante Labs Inc.

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Dante Labs Offers EUR 850 Whole Genome Sequencing and ... - PR Newswire (press release)