Editing Genes In Human Embryos

Two new CRISPR tools overcome the scariest parts of gene editing.The ability to edit RNA and individual DNA base pairs will make gene editing much more precise. Several years ago, scientists discovered a technique known as CRISPR/Cas9, which allowed them to edit DNA more efficiently than ever before.
Since then, CRISPR science has exploded; it’s become one of the most exciting and fast-moving areas of research, transforming everything from medicine to agriculture and energy. In 2017 alone, more than 14,000 CRISPR studies were published.

But here’s the thing: CRISPR, while a major leap forward in gene editing, can still be a blunt instrument. There have been problems with CRISPR modifying unintended gene targets and making worrisome, and permanent, edits to an organism’s genome. These changes could be passed down through generations, which has raised the stakes of CRISPR experiments — and the twin specters of “designer babies” and genetic performance enhancers — particularly when it comes to editing genes in human embryos.
So while CRISPR science is advancing quickly, scientists are still very much in the throes of tweaking and refining their toolkit. And on Wednesday, researchers at the Broad Institute of MIT and Harvard launched a coordinated blitz with two big reports that move CRISPR in that safer and more precise direction.
In a paper published in Science, researchers described an entirely new CRISPR-based gene editing tool that targets RNA, DNA’s sister, allowing for transient changes to genetic material. In Nature, scientists described how a more refined type of CRISPR gene editing can alter a single bit of DNA without cutting it — increasing the tool’s precision and efficiency.

The first paper, out Wednesday in Science, describes a new gene editing system. This one, from researchers at MIT and Harvard, focuses on tweaking human RNA instead of DNA.

Our cells contain chromosomes made up of chemical strands called DNA, which carry genetic information. Those genes have recipes for proteins that lead to a bunch of different traits. But to carry out the instructions in any one recipe, DNA needs another type of genetic material called RNA to get involved.

RNA is ephemeral: It acts like a middleman, or a messenger. For a gene to become a protein, that gene has to be transcribed into RNA in the cell, and the RNA is then read to make the protein. If the DNA is permanent — the family recipe book passed down through generations — the RNA is like your aunt’s scribbled-out recipe on a Post-It note, turning up only when it’s needed and disappearing again.

With the CRISPR/Cas9 system, researchers are focused on editing DNA. (For more on how that system works, read this Vox explainer.) But the new Science paper describes a novel gene editing tool called REPAIR that’s focused on using a different enzyme, Cas13, to edit that transient genetic material, the RNA, in cells. REPAIR can target specific RNA letters, or nucleosides, that are involved in single-base changes that regularly cause disease in humans.

This is hugely appealing for one big reason: With CRISPR/Cas9, the changes to the genome, or the cell’s recipe book, are permanent. You can’t undo them. With REPAIR, since researchers can target single bits of ephemeral RNA, the changes they make are transient, even reversible. So this system could fix genetic mutations without actually touching the genome (like throwing away your aunt’s Post-It note recipe without adding it to the family recipe book).

Source: https://www.vox.com/

Nanofiber For Bullet Proof Vests

Harvard researchers have developed a lightweight, portable nanofiber fabrication device that could one day be used to dress wounds on a battlefield or dress shoppers in customizable fabrics. There are many ways to make nanofibers. These versatile materials — whose target applications include everything from tissue engineering to bullet proof vests — have been made using centrifugal force, capillary force, electric field, stretching, blowing, melting, and evaporation.

Each of these fabrication methods has pros and cons. For example, Rotary Jet-Spinning (RJS) and Immersion Rotary Jet-Spinning (iRJS) are novel manufacturing techniques developed in the Disease Biophysics Group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering. Both RJS and iRJS dissolve polymers and proteins in a liquid solution and use centrifugal force or precipitation to elongate and solidify polymer jets into nanoscale fibers. These methods are great for producing large amounts of a range of materials – including DNA, nylon, and even Kevlar – but until now they haven’t been particularly portable.

The Disease Biophysics Group recently announced the development of a hand-held device that can quickly produce nanofibers with precise control over fiber orientation. Regulating fiber alignment and deposition is crucial when building nanofiber scaffolds that mimic highly aligned tissue in the body or designing point-of-use garments that fit a specific shape.

nanofiber

Our main goal for this research was to make a portable machine that you could use to achieve controllable deposition of nanofibers,” said Nina Sinatra, a graduate student in the Disease Biophysics Group and co-first author of the paper. “In order to develop this kind of point-and-shoot device, we needed a technique that could produce highly aligned fibers with a reasonably high throughput.

The new fabrication method, called pull spinning, uses a high-speed rotating bristle that dips into a polymer or protein reservoir and pulls a droplet from solution into a jet. The fiber travels in a spiral trajectory and solidifies before detaching from the bristle and moving toward a collector. Unlike other processes, which involve multiple manufacturing variables, pull spinning requires only one processing parameter — solution viscosity — to regulate nanofiber diameter. Minimal process parameters translate to ease of use and flexibility at the bench and, one day, in the field.

The research was published recently in Macromolecular Materials and Engineering.

Source: https://www.seas.harvard.edu/

Injectable 3D Vaccine Fights Cancer and HIV

One of the reasons cancer is so deadly is that it can evade attack from the body’s immune system, which allows tumors to flourish and spread. Scientists can try to induce the immune system, known as immunotherapy, to go into attack mode to fight cancer and to build long lasting immune resistance to cancer cells. Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard’s School of Engineering and Applied Sciences (SEAS) show a non–surgical injection of programmable biomaterial that spontaneously assembles in vivo into a 3D structure could fight and even help prevent cancer and also infectious disease such as HIV. Their findings are reported in Nature Biotechnology.

dentritic cells
A microscope image shows many of the immune system’s dendritic cells that were collected from a 3D scaffold three days after in vivo injection. The 3D scaffold effectively recruits and activates the dendritic cells to trigger an immune response against specific cells, such as cancerous cells

We can create 3D structures using minimally–invasive delivery to enrich and activate a host’s immune cells to target and attack harmful cells in vivo,” said the study’s senior author David Mooney, Ph.D., who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard SEAS. “Nano–sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron–sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells,” said co-lead author Jaeyun Kim, Ph.D., an Assistant Professor of Chemical Engineering at Sungkyunkwan University (Korea) and a former Wyss Institute Postdoctoral Fellow.
Source: http://wyss.harvard.edu/

How To Create Artificial Nano Flowers

With the hand of nature trained on a beaker of chemical fluid, the most delicate flower structures have been formed in a Harvard laboratory—and not at the scale of inches, but microns. These minuscule sculptures, curved and delicate, don’t resemble the cubic or jagged forms normally associated with crystals, though that’s what they are. Rather, fields of carnations and marigolds seem to bloom from the surface of a submerged glass slide, assembling themselves a molecule at a time.By simply manipulating chemical gradients in a beaker of fluid, Wim L. Noorduin, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences (SEAS) and lead author of a paper appearing on the cover of Science, has found that he can control the growth behavior of these crystals to create precisely tailored structures.
nano tulip
For at least 200 years, people have been intrigued by how complex shapes could have evolved in nature. This work helps to demonstrate what’s possible just through environmental, chemical changes,” says Noorduin.
Source: https://www.seas.harvard.edu/

Revolutionary Ultrathin, Flat Lens

Applied physicists at the Harvard School of Engineering and Applied Sciences (SEAS) have created an ultrathin, flat lens that focuses light without imparting the distortions of conventional lenses. At a mere 60 nanometers thick, the flat lens is essentially two-dimensional, yet its focusing power approaches the ultimate physical limit set by the laws of diffraction.
Operating at telecom wavelengths (i.e., the range commonly used in fiber-optic communications), the new device is completely scalable, from near-infrared to terahertz wavelengths, and simple to manufacture. The results have been published online in the journal Nano Letters.

A new ultrathin, flat lens focuses light without imparting the optical distortions of conventional lenses.

Our flat lens opens up a new type of technology,” says principal investigator Federico Capasso, Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS. “We’re presenting a new way of making lenses. Instead of creating phase delays as light propagates through the thickness of the material, you can create an instantaneous phase shift right at the surface of the lens. It’s extremely exciting.
This breakthrough could lead to smart phones as thin as a credit card. “In the future we can potentially replace all the bulk components in the majority of optical systems with just flat surfaces,” says lead author Francesco Aieta, a visiting graduate student from the Università Politecnica delle Marche in Italy. “It certainly captures the imagination.”

Source: http://www.seas.harvard.edu/news-events/press-releases/flat-lens-offers-perfect-image

Supramolecular Nanochemistry To Fight Tumors

Researchers at Brigham and Women's Hospital (BWH), affiliate to Harvard Medical School,  are the first to report a new approach that integrates rational drug design with supramolecular nanochemistry in cancer treatment. Supramolecular chemistry is the development of complex chemical systems using molecular building blocks. The researchers utilized such methods to create nanoparticles that significantly enhanced antitumor activity with decreased toxicity in breast and ovarian cancer models

 

"This work is effectively moving beyond using nanotechnology as drug 'delivery' vehicles to reengineering drugs themselves so that they become nanomedicines." said Shiladitya Sengupta, PhD, MSc, BWH associate bioengineer, and senior study author . 

Source: http://www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?PageID=%201212