Extended genetic alphabet covered in New York Times

DNA Gets a New — and Bigger — Genetic Alphabet

DNA is spelled out with four letters, or bases. Researchers have now built a system with eight. It may hold clues to the potential for life elsewhere in the universe and could also expand our capacity to store digital data on Earth.

In 1985, the chemist Steven A. Benner sat down with some colleagues and a notebook and sketched out a way to expand the alphabet of DNA. He has been trying to make those sketches real ever since.

On Thursday, Dr. Benner and a team of scientists reported success: in a paper, published in Science, they said they have in effect doubled the genetic alphabet.

Natural DNA is spelled out with four different letters known as bases — A, C, G and T. Dr. Benner and his colleagues have built DNA with eight bases — four natural, and four unnatural. They named their new system Hachimoji DNA (hachi is Japanese for eight, moji for letter).

Crafting the four new bases that don't exist in nature was a chemical tour-de-force. They fit neatly into DNA’s double helix, and enzymes can read them as easily as natural bases, in order to make molecules.

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Crispr Therapeutics AG has treated its first human

Crispr Infuses First Human in Landmark Gene-Editing Study

Crispr Therapeutics AG  shares surged after the company said it has treated the first human with the same genetic technology that shares its name in an early-stage study.

Crispr Therapeutics and partner Vertex Pharmaceuticals Inc. said on Monday morning that the first patient in a trial using CTX001, a therapy created using Crispr technology, as a treatment for the rare blood disease, beta thalassemia, received the one-time medicine. The pair also announced the enrollment of the first patient has started in a parallel study for the medicine in sickle-cell disease with the first dosing on track for mid-year.

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New DNA repair mechanism identified

Novel DNA repair mechanism preserves genome integrity

"I'm just astounded," said Cortez, Ingram Professor of Cancer Research and professor of Biochemistry. The investigators, led by postdoctoral fellow Kareem Mohni, Ph.D., have discovered a new DNA repair mechanism.

"DNA repair is a very mature field. The Nobel Prize was given a few years ago to three scientists who studied DNA repair in the 1970s and 80s," Cortez said.

"People are still very interested in DNA repair, and there are important questions that we're asking, but the idea of finding a whole new repair mechanism … nobody would have thought this is possible."

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CRISPR Gene Editing advances

Gene Editing is trickier THAN expected—BUT fixes are in sight

Of all the big, world-remaking bets on the genome-editing tool known as Crispr, perhaps none is more tantalizing than its potential to edit some of humanity’s worst diseases right out of the history books. Just this week, Crispr Therapeutics announced it had begun treating patients with an inherited blood disorder called beta thalassemia, in the Western drug industry’s first test of the technology for genetic disease. But despite the progress, there remain a host of unknowns standing in the way of Crispr-based medicines going mainstream, chief among them safety.

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World Health Organization might make some human genome editing rules

Human genome editing is here – now we have to decide who is in charge

The World Health Organization (WHO) will convene a meeting this month to develop global standards of governance for human genome editing. This is a welcome move. Although the committee has no powers to enforce compliance – it is still a matter for individual nations to decide on regulations, with China reportedly updating its rules earlier this week – the WHO committee’s recommendations will be influential and far-reaching in their ambition. But I hope committee members will bear a few points in mind in their discussions.

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Synthetic DNA is a new technology and probably needs some new rules

Opinion: Ethical Boundaries Needed on the Uses of Synthetic DNA

A newly expanded genetic alphabet that includes four synthetic nucleotides highlights the need for strict boundaries on their use.

A study published last week expands the redesign of the 4-billion-year-old genetic code from a four-nucleotide base-pair alphabet to an eight-base-pair alphabet by incorporating artificial nucleotides. The scientists, led by Steven Benner of the Foundation for Applied Molecular Evolution and Firebird Biomolecular Sciences in Florida, have also identified a bacteriophage RNA polymerase variant that transcribes the synthetic DNA into synthetic RNA.  

Previously, a scientific team led by Floyd Romesberg at The Scripps Research Institute used its own synthetic base pairs to create bacteria that replicate the artificial DNA, translate the DNA into mRNA, and create new types of amino acids. 

These are technologically impressive accomplishments and the translational applications of these discoveries could be revolutionary.

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Four new bases available for synthetic biology (original article)

Hachimoji DNA and RNA: A genetic system with eight building blocks

Expanding the genetic code

DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hoshika et al. added an additional four synthetic nucleotides to produce an eight-letter genetic code and generate so-called hachimoji DNA. Coupled with an engineered T7 RNA polymerase, this expanded DNA alphabet could be transcribed into RNA. Thus, new forms of DNA that add information density to genetic biopolymers can be generated that may be useful for future synthetic biological applications.

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A European take on CRISPR corn

Boosting corn yields with CRISPR-carrying pollen

Scientists have developed a single-step gene editing process that can increase corn yields.
The new technique uses pollen to transfer the components of CRISPR-Cas9 into another plant allowing them to produce gene edited corn, a process previously hindered by the thick cell walls of many plants, such as corn and wheat. Results of the first set of experiments were published on 4 March in Nature Biotechnology.

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CRISPR quality improvement tested

CRISPR Base Editor Takes Diagnostic and Remedial Exams

Whether a CRISPR-based editing tool makes the grade or needs remedial work isn’t clear until it is subjected to testing, thorough and systematic testing. Consequently, scientists based at South Korea’s Institute for Basic Science (IBS) are administering the CRISPR equivalent of standardized tests. Rather than present CRISPR tools with a #2 pencil and a fill-in-the-oval sheet, the scientists provide different guide RNAs. Then the scientists use genome sequencing to check for errors such as off-target effects.

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CRISPR off-target errors

A CRISPR spin-off causes unintended typos in DNA

Even the best editor sometimes introduces typos. That’s true whether the editor is human or a version of the much-heralded gene-editing tool CRISPR.

One type of CRISPR gene editor that changes individual DNA bases, rather than cutting DNA, introduces more unwanted mutations than expected in mouse embryos and rice plants, researchers report. Those mistakes occurred in places where the tool wasn’t supposed to make changes. Another tested base editor, however, didn’t make the undesirable edits. The results were described in two studies published online February 28 in Science.

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CRISPR ups corn yields

Scientists Use CRISPR on Edit-Resistant Corn to Boost Yields

Scientists have used pollen carrying CRISPR/Cas9 to genetically edit hard-to-edit crops like corn, opening the door to new ways to boost important crop yields.

CRISPR/Cas9 Used on Edit-Resistant Corn Crops 

Scientists at the North Carolina-based agricultural firm Syngenta have discovered a novel way to use CRISP/cas9 gene-editing techniques on important varieties of corn that have proven especially resistant to the process, according to Science magazine.

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Improved CRISPR efficiency in DMD treatment

Scientists find method to boost CRISPR efficiency

Scientists have developed a method to boost the efficiency of CRISPR gene editing in Duchenne muscular dystrophy (DMD), according to a study that could have implications for optimizing gene therapies for other diseases.

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China claims it will tighten rules on human genetic engineering

China to tighten rules on gene editing in humans

China’s health ministry has issued draft regulations that will restrict the use of gene editing in humans, just three months after Chinese researcher He Jiankui announced that twin girls had been born with edited genomes. The proposal includes severe penalties for those who break the rules. If approved, scientists say the policy could have gains and drawbacks for research.

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Non-small cell lung cancer prognosis from blood samples

Tumor DNA in blood may predict response to lung-cancer immunotherapy

Blood tumor mutational burden may give insight into which patients with non-small cell lung cancer (NSCLC) may benefit from therapy with anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibodies, according to Chinese researchers.

A considerable number of patients with advanced cancer may not be able to provide sufficient tissue for molecular testing to guide treatment decisions, Dr. Jie Wang of Peking Union Medical College and colleagues note in JAMA Oncology, online February 28. However, rather than use tumor mutational burden measured by whole-exome sequencing or cancer gene panel, the researchers sought to determine the utility of using circulating tumor DNA in blood.

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(CAR)-T treatment for Lupus looks promising

Genetically engineered immune cells wipe out lupus in mice

Lupus can be a stubborn disease to treat. Although many struck by the autoimmune condition live relatively normal lives, some suffer from kidney failure, blood clots, and other complications that can be deadly. Now, scientists have found that a novel treatment that wipes out the immune system’s B cells cures mice of the condition. Though the work is preliminary, it has excited researchers because it uses a therapy already approved for people with blood cancer.

The strategy is known as chimeric antigen receptor (CAR)-T therapy. 

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World Economic Forum weighs in on CRISPR

Editing the human genome: do the risks outweigh the rewards?

In November last year, the international scientific community was shocked by the announcement by He Jiankui, a CRISPR scientist, that he and his team at the Southern University of Science and Technology in Shenzhen had created the first “gene-edited babies”. The genetic material of these babies had been edited to make them resistant to HIV, smallpox and cholera.

This event has raised a flurry of reactions and controversies, and also demonstrated some deep ambiguities surrounding the risks and implications of research on genome editing, which could fundamentally change how humans are “fabricated”. Beyond the purely scientific aspect, the question of how to balance potential benefits against the potential negative consequences must consider the acceptability of the risks involved.

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RNA-seq advances aim to get it all

Taming the RNA Zoo While Saving Rare Transcripts

The lab is no wildlife park for RNA, but life sciences researchers can capture and display low-abundance, unstable, and otherwise vulnerable species

RNA analysis would do well to follow the example set by naturalists, scientists who patiently add new species to their catalogs while remembering that any catalog, however comprehensive, is of limited interest. What really matters, in botany or zoology or, more pertinently, RNA biology, is learning how species impact each other and fulfill their environmental roles.

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Potential of CAR T

Custom CAR T Cells Made to Order

Chimeric antigen receptor (CAR) T cells are about as cutting-edge as cancer care gets today. Having demonstrated the ability to eradicate tumor cells in up to 90% of patients with certain blood cancers, these engineered immune cells became the first class of gene therapy to win FDA approval in 2017—with Novartis’ Kymriah getting the nod in August, followed by Kite Therapeutics’ Yescarta in October.3 But Alexander Marson, MD, PhD, knows these sophisticated cells are capable of so much more.

Marson, an immunologist at the University of California at San Francisco, is exploring this potential by using the CRISPR-Cas9 system to introduce precisely targeted genome modifications. The idea is that by adding or deleting specific genomic sequences, one can make these cells more lethal for tumors but also safer for the patient. Marson’s team recently developed a platform called SLICE4—single-guide RNA (sgRNA) lentiviral infection with Cas9 protein electroporation—to perform diverse CRISPR modifications in many cells in parallel, in hopes of rapidly identifying changes that measurably improve CAR T-cell performance. “We’re pretty good at manufacturing the ‘hardware’ of gene edited cells, and we’re continuing to improve that,” says Marson. “The really interesting thing will be what genetic ‘software’ we can put into them.”

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China's CRISPR twins raise possibility of far off-target effects

China’s CRISPR twins might have had their brains inadvertently enhanced

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories.

The brains of two genetically edited girls born in China last year may have been changed in ways that enhance cognition and memory, scientists say.

The twins, called Lulu and Nana, reportedly had their genes modified before birthby a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS.

Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

BEAM invests in CRISPR-based therapeutics

Beam Brings In $135M to Turn CRISPR Base Editing into Drugs

Xconomy Boston — Beam Therapeutics made a splash last year when it launched with $87 million to develop medicines that use a more precise form of CRISPR editing. Beam’s promise of CRISPR-based therapeutics that swap out specific bases or “letters” in the genome—something the current generation of CRISPR-based drugs can’t do—has been so enticing to investors that they have put in $135 million in a Series B investment less than a year after the first funding round.

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