SynBioFromLeukipposInstitute

Scientists in Boston have come up with a twist on an important method for “editing” genomes that could give researchers added control over the DNA of living things and influence a raging patent dispute over the powerful techniques.

Feng Zhang, a researcher at the Broad Institute of MIT and Harvard, reported today in the journal Cell that he had developed a replacement for a key component of the genome-engineering system commonly known as CRISPR-Cas9.

The gene-editing technology, which snips DNA at precise locations, has swept through science labs because it provides a versatile, potent way to engineer the DNA of bacteria, plants, and humans. It is allowing scientists to broadly reimagine how they study everything from Alzheimer’s disease to biotech crops.

The work by Zhang’s team, carried out this year, shows that the cutting protein Cas9 can be replaced by a different protein, Cpf1, which he says will also work as a versatile editing tool. In a carefully crafted press release, Broad chief Eric Lander said the system “represents a new generation of genome editing technology” that has “dramatic potential to advance genetic engineering.”

IF YOU WANT to drop some real DNA editing knowledge—like, I don’t know, at a party!—here’s a tip. Instead of calling the much hyped precise genome-editing tool CRISPR, call it CRISPR/Cas9. CRISPR, you see, just refers to stretches of repeating DNA that sit near the gene for Cas9, the actual protein that does the DNA editing.

Well, at least for now. Today, gene-editing scientists dropped some curious news: They’ve found a CRISPR system involving a different protein that also edits human DNA, and, in some cases, it may work even better than Cas9.

The discovery comes at a time when CRISPR/Cas9 is sweeping through biology labs. So revolutionary is this new genome editing technique that rival groups, who each claim to have been first to the tech, are bitterly fighting over the CRISPR/Cas9 patent. This new gene-editing protein called Cpf1—and maybe even others yet to be discovered—means that one patent may not be so powerful after all.

And there’s good reason to think more useful CRISPR proteins are out there. CRISPR sequences are a part of primordial immune systems, found in some 40 percent of bacteria and 90 percent of archaea. In a study published today in Cell, Feng Zhang (no relation to this writer) and colleagues trawled through bacterial genomes looking for different versions of Cpf1. They found two, from Acidominococcus and Lachnospiraceae, that can snip DNA when scientists insert them into human cells.

“There are definitely many more defense systems out there, and maybe some of them might even have spectacular applications like with the Cas9 system,” says John van der Oost, a microbiologist at Wageningen University who is a co-author on the paper. “We have the feeling it’s just the tip of the iceberg.”

Zhang and van der Oost’s search was deliberate, but the initial discovery of CRISPR/Cas9 as a gene-editing tool was not. Back in the 1980s, microbiologists saw strange repeating sequences in the DNA of bacteria. Those clustered regularly interspaced short palindromic repeats became CRISPR, and scientists realized they were evidence of an immune system bacteria used to defend against viruses. The spacers between the repeats are in fact snippets of viral genomes, which CRISPR-associated proteins called Cas use as “mug shots” to recognize viruses and shred their DNA.

Many different proteins are associated with CRISPR. But in the early 2010s, Emmanuelle Charpentier, who was studying the flesh-eating bacteria Streptococcus pyogenes, stumbled onto one with special powers. Her bacteria happen to carry Cas9 proteins, which have the remarkable ability to precisely cut DNA based on a RNA guide sequence. In 2012, Charpentier and UC Berkeley biologist Jennifer Doudna published a paper describing the CRISPR/Cas9 system and speculated about its genome editing capabilities. And they filed a patent application. Much more on that patent later.

Long ago, a clan of hardy microbes called cyanobacteria helped terraform the lifeless Earth into a vibrant biosphere. Today, the very same critters could be the key to colonizing Mars.

Plants are going to have a tough time on the Red Planet’s hostile surface, but cyanobacteria have coped with extreme environments for eons. A paper led by astrobiologist Cyprien Verseux of NASA’s Ames Research Institute argues that we can harness these tiny photosynthesis machines to produce many of the resources we’ll need to survive, from food and oxygen to metals and medicine. Here are all the ways cyanobacteria can help us build a Martian colony.

Extracting Elements

In science fiction, we find humans harvesting fields of wheat under terraformed Martian skies and growing rows of potatoes inside climate-controlled Habs. But in reality, growing any plants on Mars is going to be a challenge, because the Martian soil lacks some key ingredients.

Interview Subject: Alexandra Daisy Ginsberg: Designer, Artist, Writer, and PhD Researcher in Design Interactions at the Royal College of Art

Tell me about your interest in design. Did you know, when you were nine years old, that you were an artist or a designer and you wanted to go in that direction? Or was it a circuitous route?
I wanted to be an artist (my grandmother is a sculptor, it seemed a very good job, involving welding, tools and lots of mess), then briefly, a product designer. I chose to study architecture at university, then worked in urbanism, and then ended up going to design school. It’s been a winding path! I also considered studying politics, philosophy and economics at one point, and now those areas are resurfacing in my research.

Fifteen years ago, scientific instigator J. Craig Venter spent $100 million to race the government and sequence a human genome, which turned out to be his own. Now, with a South African health insurer, the entrepreneur says he will sequence the medically important genes of its clients for just $250.

Human Longevity Inc. (HLI), the startup Venter launched in La Jolla, California, 18 months ago, now operates what’s touted as the world’s largest DNA-sequencing lab. It aims to tackle one million genomes inside of four years, in order to create a giant private database of DNA and medical records.

In a step toward building the data trove, Venter’s company says it has formed an agreement with the South African insurer Discovery to partially decode the genomes of its customers, returning the information as part of detailed health reports.

The deal is a salvo in the widening battle to try to bring DNA data to consumers through novel avenues and by subsidizing the cost of sequencing. It appears to be the first major deal with an insurer to offer wide access to genetic information on a commercial basis.

Jonathan Broomberg, chief executive of Discovery Health, which insures four million people in South Africa and the United Kingdom, says the genome service will be made available as part of a wellness program and that Discovery will pay half the $250, with individual clients covering the rest. Gene data would be returned to doctors or genetic counselors, not directly to individuals. The data collected, called an “exome,” is about 2 percent of the genome, but includes nearly all genes, including major cancer risk factors like the BRCA genes, as well as susceptibility factors for conditions such as colon cancer and heart disease. Typically, the BRCA test on its own costs anywhere from $400 to $4,000.

“I hope that we get a real breakthrough in the field of personalized wellness,” Broomberg says. “My fear would be that people are afraid of this and don’t want the information—or that even at this price point, it’s still too expensive. But we’re optimistic.” He says he expects as many as 100,000 people to join over several years.

With the ability to transfer a trait from one creature to another purposefully, synthetic biology is advancing across unforeseen domains. From algae cells that convert carbon dioxide to fuel, biocementation bacteria to terraform mars, and lab-grown meat, synthetic biology offers new materials for designers, technologists, and artists to explore, and yet, public opinion lags behind these scientific advancements. Anytime science advances faster than our ability to apprehend it, it produces progress but also fear, suspicion and uncertainty. Amino -- an object that allows direct interaction with microorganisms to experiment with biology as material -- sets out not simply to educate but to also be part of the early culture that metabolizes the changes underway. Amino is a design driven mini-lab that allows users to carry out a bacterial transformation and enables the subsequent care and feeding of the cells that are grown. Inspired by Tamagotchis, the genetic transformation of an organism's DNA is performed by the user through guided interactions, resulting in their synthetic organism for which they can care like you would a pet. Amino is developed using low cost ways of carrying out lab-like procedures in the home and is packaged in a suitcase-sized continuous bioreactor for cells.

The CRISPR/Cas9 technique is revolutionizing genetic research: Scientists have already used it to engineer crops, livestock and even human embryos, and it may one day yield new ways to treat disease.

But now one of the technique's pioneers thinks that he has found a way to make CRISPR even simpler and more precise. In a paper published in Cell on 25 September, a team led by synthetic biologist Feng Zhang of the Broad Institute in Cambridge, Massachusetts, reports the discovery of a protein1 called Cpf1 that may overcome one of CRISPR-Cas9’s few limitations; although the system works well for disabling genes, it is often difficult to truly edit them by replacing one DNA sequence with another.

The CRISPR/Cas9 system evolved as a way for bacteria and archaea to defend themselves against invading viruses. It is found in a wide range of these organisms, and uses an enzyme called Cas9 to cut DNA at a site specified by 'guide' strands of RNA. Researchers have turned CRISPR/Cas9 into a molecular-biology powerhouse that can be used in other organisms. The cuts made by the enzyme are repaired by the cell’s natural DNA-repair processes.

If news stories pertaining to pharmaceutical drugs have got you down, here's something to perk you up: Duke University scientists have successfully hacked the genetic code controlling how and when proteins self-assemble and disassemble. It's a huge step forward for designer proteins, synthetic biology, and a whole host of other future-minded pieces of medical research. Perhaps most importantly, these findings may result in new and effective ways to deliver drugs to vital areas within the body.

A genomic entrepreneur plans to sell genetic workups for as little as $250. But $25,000 gets you “a physical on steroids.”

In 1999, 19-year-old Sean Ward created one of the first music-recommendation algorithms, dropped out of the University of Virginia, and started his own company. By age 25, he had tired of the conflict between record companies and Internet users, so he turned to something completely different: bioengineering.
“In many respects, genetic engineering is the ultimate remix technology,” Ward says. Bioengineers copy DNA from one organism and adapt it for another to create life-forms that change color, glow, or produce new medicine or materials. In today’s high-speed, high-volume biolabs, automated tools like pipetting robots do most of the work—and each requires different kinds of code. Ward saw that, like music, biotech research had become digital. And also as with music, he could use his programming skills to give more people access to it.
This past November, Ward’s company, Synthace, released Antha, the first open-source programming language that works across different biotech machines. Anyone who can code can write commands in Antha to direct all of a lab’s equipment. This allows researchers—or programmers with a yen for genetic engineering—to more easily perform complex experiments, and share how they did it.
Ward was one of the first to see the potential of DIY genetic engineering, but he’s not the last. Other companies are now producing tools that make it possible for amateurs to create new organisms—or, in Ward’s words, to “program the assembly of matter.”