Toward CRISPR 2.0

In two papers published on the same day, October 25, in Science and Nature, two research teams at MIT, Harvard, the Broad Institute of MIT and Harvard, and Howard Hughes Medical Institute (HHMI), have described new powerful molecular gene editors (see below), an RNA editor and a DNA base editor that swaps base pairs.

Both advances are covered in a Nature News commentary, titled “CRISPR hacks enable pinpoint repairs to genome,” and an MIT Technology Review commentary, titled “CRISPR 2.0 Is Here, and It’s Way More Precise.” Compared to many important scientific news items, these genome editing breakthroughs have been widely covered by the mainstream and popular press.

“A paper published this week describes means of [altering specific bases without cutting the DNA strands they are in], namely programmable protein machines called base editors that rearrange the atoms of one base so that it becomes another,” The Economist reports. “And another paper describes how to achieve a similar ultimate outcome - a change in the protein encoded by a gene - but in a way that does not involve DNA directly at all.”

“The new RNA-editing system, which the scientists have dubbed Repair, allows the editing of individual RNA letters, correcting a common mutation known to play a role in a number of diseases,” notes The Wall Street Journal. “To test whether Repair works, in the lab the researchers created the mutations that lead to two diseases, Fanconi anemia and X-linked nephrogenic diabetes insipidus, introduced the mutations in human cells, and used the Crispr-based Repair system to correct the RNA.”

How to REPAIR RNA. Scientists at MIT and Broad Institute have developed a new CRISPR-based system, called RNA Editing for Programmable A to I Replacement, or “REPAIR.” The system, described in a study published in Science, can change single RNA nucleotides in mammalian cells in a programmable and precise fashion. REPAIR has the ability to reverse disease-causing mutations at the RNA level, as well as other potential therapeutic and basic science applications.

Molecular pencils for fine-tuned DNA surgery. Researchers at Harvard, Broad Institute and Howard Hughes Medical Institute (HHMI) have built an enzyme that can perform a previously impossible DNA swap, directly changing the DNA base pair from an A-T to a G-C as described in a research paper published in Nature. Last year, the same researchers described a base editor that could perform the reverse operation, changing C-G base pairs into T-A. According to the scientists, base editors are more precise than comparatively “coarse” CRISPR applications, and able to act as “molecular pencils” that may one day enable fine-tuned “genome surgery” to erase harmful mutations and write helpful ones.

DNA-laced hydrogel for drug delivery and future medical applications. Researchers at Penn State have developed a DNA-laced hydrogel that can receive a chemical signal and release the appropriate protein. This biomimetic hydrogel system, described in a study published in Chemical Science, could be a general platform for versatile potential applications such as drug delivery, cell regulation, molecular sensing, and regenerative medicine. The researchers plan to use the new system for controlled drug delivery and other biological actions.

Precise electrical brain stimulation could enhance memory. Scientists at UCLA have discovered where and how to electrically stimulate the human brain to enhance people’s recollection of distinct memories. A study published in eLife suggests that even low currents of electricity can affect the brain circuits that control memory and human learning. It also illustrates the importance of precisely targeting the stimulation to the right entorhinal region. The researchers report that people with epilepsy who received low-current electrical pulses showed a significant improvement in their ability to recognize specific faces and ignore similar ones.

Cellular “mechanical memory” in metastatic tumors. Researchers at Washington University in St. Louis have investigated “mechanical memory” processes in cells that move around the body, for example to heal wounds or to form cancerous metastases, with a device that mimics a tumor environment in the body. A research paper published in Biomaterials shows that cells remember the properties they had in a previous environment for several days after they move to a new environment. According to the scientists, the research could lead to a better understanding of cancer metastatic processes.