Genetic Engineering

Biohacker Attempts Editing His DNA With CRISPR

From This Guy Says He’s The First Person To Attempt Editing His DNA With CRISPR

the biohacker claims he’s the first person trying to modify his own genome with the groundbreaking gene-editing technology known as CRISPR. And he’s providing the world with the means to do it, too, by posting a “DIY Human CRISPR Guide” online and selling $20 DNA that promotes muscle growth.

But editing your DNA isn’t as simple as following step-by-step advice. Scientists say that injecting yourself with a gene for muscle growth, as Zayner’s done, won’t in fact pump up your arms. Zayner himself admits that his experiments over the last year haven’t visibly changed his body. There are safety risks, too, experts say: People could infect themselves, or induce an inflammatory reaction.

But to Zayner, whether or not the experiment actually works is besides the point. What he’s trying to demonstrate, Zayner told BuzzFeed News, is that cutting-edge biology tools like CRISPR should be available to people to do as they wish, and not be controlled by academics and pharmaceutical companies.

The point is not if it’s legit or not, effective or not, legal or not. The point is that there is a growing community of humans that is experimenting, tinkering, and taking risks with their bodies, trying to achieve things that the mainstream audience considers horrifying, impossible, out of reach. This community doesn’t have much credibility today, just like IT security hackers didn’t have much credibility in the early days of the Internet. Today, hacking communities are recruiting pools by top military organizations in the world, and hacking conferences are a prime stage for the biggest software and hardware vendors on the market.

Lost in a sea of pseudo-scientists, impostors, scammers, and amateur wannabe, there are a few serious, determined, fearless explorers of the human body. They won’t look credible until they will.

Cancer incidence increasing globally: The role of relaxed natural selection

From Cancer incidence increasing globally: The role of relaxed natural selection – You – 2017 – Evolutionary Applications

Cancer incidence increase has multiple aetiologies. Mutant alleles accumulation in populations may be one of them due to strong heritability of many cancers. The opportunity for the operation of natural selection has decreased in the past ~150 years because of reduction in mortality and fertility. Mutation-selection balance may have been disturbed in this process and genes providing background for some cancers may have been accumulating in human gene pools. Worldwide, based on the WHO statistics for 173 countries the index of the opportunity for selection is strongly inversely correlated with cancer incidence in peoples aged 0–49 years and in people of all ages. This relationship remains significant when gross domestic product per capita (GDP), life expectancy of older people (e50), obesity, physical inactivity, smoking and urbanization are kept statistically constant for fifteen (15) of twenty-seven (27) individual cancers incidence rates. Twelve (12) cancers which are not correlated with relaxed natural selection after considering the six potential confounders are largely attributable to external causes like viruses and toxins. Ratios of the average cancer incidence rates of the 10 countries with lowest opportunities for selection to the average cancer incidence rates of the 10 countries with highest opportunities for selection are 2.3 (all cancers at all ages), 2.4 (all cancers in 0–49 years age group), 5.7 (average ratios of strongly genetically based cancers) and 2.1 (average ratios of cancers with less genetic background).

Cancer treatment is a ‘double-edged sword’ by allowing survivors to pass on their tumour-causing genes

From Cancer treatment lets survivors pass on their tumour genes | Daily Mail Online

Because of the quality of our healthcare in western society, we have almost removed natural selection as the “janitor of the gene pool”.
‘Natural selection in the past had an ample opportunity to eliminate defective genes introduced by mutations.
He said: ‘However, natural selection has been significantly reduced in the past 100 to 150 years, and the direct consequence of this process is that nearly every individual born into a population can pass genes to the next generation, while some 150 years ago, only 50 per cent or less of individuals had this chance.
‘Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.
‘Allowing more people with cancer genes [to] survive may boost cancer gene accumulation. Patients who survive it will have a chance to pass this predisposition to the next generation.

and

Rather than just removing cancers, the researchers add patients should undergo genetic engineering that ‘turns off’ their tumour-causing genes.
Professor Henneberg added: ‘Assuming that the increasing genetic load underlies cancer incidence as one of the contributing factors, the only way to reduce it remains genetic engineering- repair of defective portions of the DNA or their blockage by methylation and similar approaches.
‘These techniques, though theoretically possible, are not yet practically available.
‘They will, however, need to be developed as they provide the only human-made alternative to the disappearing action of natural selection’.

Fascinating perspective and research. I think we are totally unequipped to understand the long-term implications of how we are changing the human body.

FDA approves First Gene Therapy That Fixes Hereditary Blindness

From The First Gene Therapy That Fixes Hereditary Blindness May Finally Get FDA Approval

Gene therapy typically uses an engineered virus to administer a patient with a faulty gene with a corrected version. Rather than simply responding to the symptoms of the condition in question, it attempts to make changes to the individual’s genetic make-up in order to solve the problem at its root.

Luxturna fixes a mutation in a gene known as RPE65, which is responsible for telling the body how to produce a protein that’s essential for normal eyesight. It introduces billions of engineered virus particles bearing a corrected version of the gene to the retinal cell, via a quick injection to the eyes.

however

It’s not an outright cure, and it doesn’t give recipients full 20/20 vision. There’s currently no data on how long its effects last, so there’s a chance that patients’ sight might begin to recede once again over time.

Cost is also a major factor in how accessible it is. Two of the treatment’s biggest competitors, Strimvelis and Kymriah, cost around $700,000 and $475,000 respectively.

It’s a lot of money to try something that is unlikely permanent, so at the moment this remains for very few privileged humans. But what an incredible step forward.

Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells

From Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells | bioRxiv

Biointegrated sensors can address various challenges in medicine by transmitting a wide variety of biological signals. A tempting possibility that has not been explored before is whether we can take advantage of genome editing technology to transform a small portion of endogenous tissue into an intrinsic and long-lasting sensor of physiological signals. The human skin and epidermal stem cells have several unique advantages, making them particularly suitable for genetic engineering and applications in vivo. In this report, we took advantage of a novel platform for manipulation and transplantation of epidermal stem cells, and presented the key evidence that genome-edited skin stem cells can be exploited for continuous monitoring of blood glucose level in vivo. Additionally, by advanced design of genome editing, we developed an autologous skin graft that can sense glucose level and deliver therapeutic proteins for diabetes treatment. Our results revealed the clinical potential for skin somatic gene therapy.

CRISPR used to genetically edit skin cells and turn them into a glucose detector

From Gene-Edited Skin Could Be Its Own Blood-Sugar Sensor – MIT Technology Review

To make their biological invention, Wu and team first collected from mice some of the stem cells whose job it is to make new skin. Next, they used the gene-editing technique CRISPR to create their built-in glucose detector. That involved adding a gene from E. coli bacteria whose product is a protein that sticks to sugar molecules.

Next, they added DNA that produces two fluorescent molecules. That way, when the E. coli protein sticks to sugar and changes shape, it moves the fluorescent molecules closer or further apart—generating a signal that Wu’s team could see using a microscope.

All that was done in a lab dish—so next the team tested whether the glucose-sensing cells could be incorporated into a mouse’s body by grafting the engineered skin patches onto their backs. When mice who were left hungry were suddenly given a big dose of sugar, Wu says, the cells reacted within 30 seconds. Measuring glucose this way was just as accurate as a blood test, which they also tried.

RNA targeting with CRISPR–Cas13

RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding.

After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells.

Our results establish CRISPR–Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development.

From RNA targeting with CRISPR–Cas13 : Nature : Nature Research

Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9

From Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9: Cell

Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington’s disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for diagnostic and therapeutic purposes. Here, we describe the development of a programmable CRISPR system capable of specifically visualizing and eliminating these toxic RNAs. We observe specific targeting and efficient elimination of microsatellite repeat expansion RNAs both when exogenously expressed and in patient cells. Importantly, RNA-targeting Cas9 (RCas9) reverses hallmark features of disease including elimination of RNA foci among all conditions studied (DM1, DM2, C9-ALS, polyglutamine diseases), reduction of polyglutamine protein products, relocalization of repeat-bound proteins to resemble healthy controls, and efficient reversal of DM1-associated splicing abnormalities in patient myotubes. Finally, we report a truncated RCas9 system compatible with adeno-associated viral packaging. This effort highlights the potential of RCas9 for human therapeutics.

Locana uses CRISPR to target RNA, not DNA, and address Huntington’s disease, ALS and myotonic dystrophy

From Arming Bodies with CRISPR to Fight Huntington’s Disease and ALS – MIT Technology Review

Normally, CRISPR uses a slicing protein called Cas9 that recognizes and chops up the desired DNA, eliminating a mutated gene. Yeo and his team modified Cas9 to leave DNA alone and instead bind to and cut problematic RNA.

When tested in the lab, Yeo’s CRISPR tool obliterated 95 percent or more of these RNA knots in cells harboring Huntington’s disease and a type of ALS.

The researchers also tested the approach on a form of inherited muscular dystrophy, called myotonic dystrophy. They were able to eliminate 95 percent of faulty RNAs in muscle cells taken from patients. After they applied CRISPR, the once-diseased cells resembled healthy ones. Yeo thinks more than 20 genetic diseases that are caused by toxic RNA repeats could potentially be treated this way.

Knocking down these RNAs is only temporary, though. RNA constantly regenerates, so its level in cells eventually rebounds back to normal after a few days to a week.

and

So Yeo is designing a virus capsule to carry the CRISPR machinery to the right cells. These viral delivery shuttles would allow the Cas protein to stick around in a person’s cells longer—ideally for years, turning Cas into a mini-arsenal to keep unruly RNA at bay.

Genome editing reveals a role for OCT4 in human embryogenesis

From Genome editing reveals a role for OCT4 in human embryogenesis : Nature

Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR–Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR–Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.

CRISPR has revealed a clue in how human embryos begin to develop

From CRISPR breakthrough could drop miscarriage rates | TechCrunch

CRISPR Cas9 can modify or snip out genetic defects thought to contribute to miscarriage, but until now it wasn’t clear why some embryos continued to form into a fetus and others did not.

British scientists conducting the study found that a certain human genetic marker called OTC4 played an important role in the formation and development in the early stages of embryonic development. The scientists used CRISPR Cas9 to knock out this important gene in days-old human embryos and found that without it, these embryos ceased to attach or grow properly.

The findings could not only help us better understand why some women suffer more miscarriages than others, but it could also potentially greatly increase the rate of successful in vitro fertilization (IVF) procedures.

People could be identified using their DNA to predict their physical traits

From Geneticists pan paper that claims to predict a person’s face from their DNA : Nature

Venter and colleagues at his company Human Longevity, Inc. (HLI), based in San Diego, California, sequenced the whole genomes of 1,061 people of varying ages and ethnic backgrounds. Using the genetic data, along with high-quality 3D photographs of the participants’ faces, the researchers used an artificial intelligence approach to find small differences in DNA sequences, called SNPs, associated with facial features such as cheekbone height. The team also searched for SNPs that correlated with factors including a person’s height, weight, age, vocal characteristics and skin colour.

The approach correctly identified an individual out of a group of ten people randomly selected from HLI’s database 74% of the time. The findings, according to the paper, suggest that law-enforcement agencies, scientists and others who handle human genomes should protect the data carefully to prevent people from being identified by their DNA alone.

The scientific community, including a co-author (who works for Apple), suggests that the paper misrepresented the data.

The point is that we are going in that direction and the progress is remarkable. The scientist reviewing the paper for Nature said:

HLI’s actual data are sound, and he is impressed with the group’s novel method of determining age by sequencing the ends of chromosomes, which shorten over time.

U.S. attitudes on human genome editing

From U.S. attitudes on human genome editing | Science

The emergence of CRISPR-Cas9 gene editing has given new urgency to calls from social scientists, bench scientists, and scientific associations for broad public dialogue about human genome editing and its applications. Most recently, these calls were formalized in a consensus report on the science, ethics, and governance of human genome editing released by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine (NAM) that argued for public engagement to be incorporated into the policy-making process for human genome editing (1). So, where does the public stand on the issue of human genome editing? And how do those attitudes translate into the desire for more public input on human genome editing as new applications emerge in the policy arena?

How does the public feel about editing human DNA?

From Two-thirds of Americans approve of editing human DNA to treat disease – The Verge

First of all, gene editing can mean a lot of different things: you can edit the human genome for therapeutic purposes, to treat disease, for instance; or potentially to “enhance” human abilities, such as intelligence. And those changes can be made so that they’re passed on to future generations (so-called germline editing) or so that they affect only the individual whose cells are being edited (somatic editing).

Scheufele wanted to survey the public on gene editing in all its nuances, because people may have very different opinions on whether embryos are edited to cure a crippling disease or to boost a kid’s intelligence. (None of these things have been accomplished yet; the research is still in its infancy.) And one of his findings took Scheufele by surprise: he expected people to draw a line when it comes to all kinds of germline editing. After all, edits that can be passed on to future generations can change the human gene pool forever — and we don’t really know what the consequences might be. But he found that people really only drew a line when editing, especially germline editing, was for “enhancement” rather than treating disease.

Correction of a pathogenic gene mutation in human embryos

From Correction of a pathogenic gene mutation in human embryos – Nature

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response.

Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations.

First Human Embryos Edited with CRISPR in US

From First Human Embryos Edited in U.S. – MIT Technology Review

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned. The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR

To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

One week later, additional details emerge.

From US scientists have corrected a genetic heart mutation in embryos using CRISPR | TechCrunch

Shoukhrat Mitalipov and his colleagues from Oregon Health and Science University have successfully used the CRISPR Cas9 gene editing technology to wipe out a genetically inherited heart mutation in embryos.

Mitalipov and his colleagues were able to avoid the previous mistakes made by the Chinese scientists by injecting the Cas9 enzyme (which acts as a sort of scissors for DNA fragments) into the sperm and eggs at the same time.

What an incredible moment in history to witness.

Amazon has a secret unit called 1492 focused on health tech

From Amazon 1492: secret health tech project

The stealth team, which is headquartered in Seattle, is focused on both hardware and software projects, according to two people familiar. Amazon has become increasingly interested in exploring new business in healthcare. For example, Amazon has another unit exploring selling pharmaceuticals, CNBC reported in May.

The new team is currently looking at opportunities that involve pushing and pulling data from legacy electronic medical record systems. If successful, Amazon could make that information available to consumers and their doctors.
1492 Conquer of Paradise.

I wouldn’t be surprised if long-term goal of this unit would be, just like for Google’s Verily, genetic engineering and anti-aging medical research.

New protein AcrIIA4 increases CRISPR-CAS9 precision

From This DNA-mimicking protein can make gene editing more precise and safe – The Verge

Even though gene-editing tools like CRISPR-Cas9 are very precise, they sometimes snip pieces of DNA they weren’t programmed to cut. These off-target cuts can be dangerous, and scientists have been trying to find ways to prevent them.

The researchers found that the protein AcrIIA4 mimics DNA so that it can bind to the Cas9 enzyme, blocking it from attaching to actual DNA and cutting it.

Finally, the researchers added AcrIIA4 a few hours after adding the Cas9; that prevented CRISPR from cutting DNA at the wrong sites, while still allowing time for cutting at the right sites.

New Study Demonstrates Potential for AI and Whole Genome Sequencing to Scale Access to Precision Medicine

From IBM News room – 2017-07-11 Study by New York Genome Center and IBM Demonstrates Potential for AI and Whole Genome Sequencing to Scale Access to Precision Medicine – United States

researchers at the New York Genome Center (NYGC), The Rockefeller University and other NYGC member institutions, and IBM (NYSE: IBM) bhave illustrated the potential of IBM Watson for Genomics to analyze complex genomic data from state-of-the-art DNA sequencing of whole genomes. The study compared multiple techniques – or assays – used to analyze genomic data from a glioblastoma patient’s tumor cells and normal healthy cells.

The proof of concept study used a beta version of Watson for Genomics technology to help interpret whole genome sequencing (WGS) data for one patient. In the study, Watson was able to provide a report of potential clinically actionable insights within 10 minutes, compared to 160 hours of human analysis and curation required to arrive at similar conclusions for this patient.

Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma

From Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma

Objective: To analyze a glioblastoma tumor specimen with 3 different platforms and compare potentially actionable calls from each.

Methods: Tumor DNA was analyzed by a commercial targeted panel. In addition, tumor-normal DNA was analyzed by whole-genome sequencing (WGS) and tumor RNA was analyzed by RNA sequencing (RNA-seq). The WGS and RNA-seq data were analyzed by a team of bioinformaticians and cancer oncologists, and separately by IBM Watson Genomic Analytics (WGA), an automated system for prioritizing somatic variants and identifying drugs.

Results: More variants were identified by WGS/RNA analysis than by targeted panels. WGA completed a comparable analysis in a fraction of the time required by the human analysts.

Conclusions: The development of an effective human-machine interface in the analysis of deep cancer genomic datasets may provide potentially clinically actionable calls for individual patients in a more timely and efficient manner than currently possible.

Would you start saving money for college tuition, or for printing the genome of your offspring?

From Stanford’s Final Exams Pose Question About the Ethics of Genetic Engineering | Futurism

When bioengineering students sit down to take their final exams for Stanford University, they are faced with a moral dilemma, as well as a series of grueling technical questions that are designed to sort the intellectual wheat from the less competent chaff: “If you and your future partner are planning to have kids, would you start saving money for college tuition, or for printing the genome of your offspring?”

The question is a follow up to “At what point will the cost of printing DNA to create a human equal the cost of teaching a student in Stanford?”

I’d love to see the breakdown by gender, ethnicity, etc. and how the answers evolve year over year.

The Slippery Slope Argument in the Ethical Debate on Genetic Engineering of Humans

From The Slippery Slope Argument in the Ethical Debate on Genetic Engineering of Humans | SpringerLink

This article applies tools from argumentation theory to slippery slope arguments used in current ethical debates on genetic engineering. Among the tools used are argumentation schemes, value-based argumentation, critical questions, and burden of proof. It is argued that so-called drivers such as social acceptance and rapid technological development are also important factors that need to be taken into account alongside the argumentation scheme. It is shown that the slippery slope argument is basically a reasonable (but defeasible) form of argument, but is often flawed when used in ethical debates because of failures to meet the requirements of its scheme.

Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations

From Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations | SpringerLink

This paper describes some likely semiotic consequences of genetic engineering on what Gregory Bateson has called “the mental ecology” (1979) of future humans, consequences that are less often raised in discussions surrounding the safety of GMOs (genetically modified organisms). The effects are as follows: an increased 1) habituation to the presence of GMOs in the environment, 2) normalization of empirically false assumptions grounding genetic reductionism, 3) acceptance that humans are capable and entitled to decide what constitutes an evolutionary improvement for a species, 4) perception that the main source of creativity and problem solving in the biosphere is anthropogenic. Though there are some tensions between them, these effects tend to produce self-validating webs of ideas, actions, and environments, which may reinforce destructive habits of thought. Humans are unlikely to safely develop genetic technologies without confronting these escalating processes directly. Intervening in this mental ecology presents distinct challenges for educators, as will be discussed.