Summary: Researchers have developed a new technology based on CRISPR which transports RNA to exact locations within neurons, where it can trigger repair and regrowth, offering hope to treat diseases and neurological injuries. Unlike traditional CRISPR tools that modify DNA, this system reuses CRISPR-CAS13 to act as a “factor”, transporting RNA to damaged sites using integrated molecular postal codes.
In laboratory tests, the technique, called TRISPR-TO, increased the growth of neuritis up to 50% in just 24 hours, marking a major step in the spatial medicine of RNA. This breakthrough can allow more safe and more effective RNA treatments for conditions such as ALS, spinal cord lesions and neurodegenerative disorders.
Key facts:
- CRISPR-TO system: Case13 Delivered RNA to precise neural sites using molecular postal codes.
- Improved regrowth: Favored growth in 50% higher neuritis in injured neurons.
- New medicine class: Introduce the “Space RNA drug” for targeted cell repair.
Source: Stanford
When a neuron in our body is damaged, RNA segments produce proteins that can help repair the injury. But in neurological disorders such as SLA and spinal muscular atrophy, or after spinal cord lesions, the displacement mechanisms of the RNA essential to life to sites injured in the cell fail. Consequently, RNA molecules cannot happen where they are necessary and damage becomes permanent.
Stanford researchers have developed technology to transport RNA to specific locations within a neuron, where it can repair and even push the parts of the cell.
Their work, supported by the National Institutes of Health, constitutes the basis of a new class of therapies that researchers call “spatial medicine of RNA”, which, hope, will lead to treatments for neurological diseases as well as traumatic injuries.
“For the first time, we have exploited the power of CRISPR technology to create a precise spatial” postal code “which provides RNA molecules exactly where they are necessary in the cells,” said Stanley Qi, associate professor of bio-engineering and principal author on the document published on May 21 in May 21 in Nature.
“Imagine being able to specifically target damaged sites within a neuron, repairing them and promoting their regrowth – that’s what our technology realizes.”
A factor based on CRISPR
In recent years, researchers have realized that the distribution of RNA in a cell – where are specific molecules – can be just as important as they are capable of doing.
An individual neuron can last a meter long, and aging, injuries and mutations can all disturb its ability to transport the tiny RNA over such a distance.
“Therapeutic RNA cannot help if it does not happen where it is necessary,” said Qi. “We wanted to create a technology that could reliably move RNA to the place where it should work.”
Qi and his colleagues used a version of the CRISPR gene editing tool, called CRISPR-CAS13, to target individual RNA parts (unlike the more widely known CRISPR-CAS9, which targets DNA).
As a rule, CRISPR is used to decide and modify the genetic code, but in this case, the researchers did not want to make changes. They just wanted to move the existing RNA to a new place in the cell.
“Case13 acts naturally as a pair of scissors, but we have designed it to act as a factor instead,” said Qi.
“Then we can tell him to transport the RNA from one precise location to another.”
The researchers twinned case13 with specific location signals which act as addresses, instructing the case13 where to deliver the RNA. Each location in the cell has its own address molecule, so that researchers can direct the RNA to various places by adding different molecules to the cell.
Qi and his colleagues used their technology, which they call TRISPR-TO, to project dozens of RNA pieces and see if one of them would help neurons develop.
They added TRISPR -TO to the brain neurons of mouse in a petri box, where he transported the RNA molecules to the tips of the neuritis – the finger -shaped protuberances that form synapses and connect to other neurons.
They found several promising candidates, including a RNA molecule which increased the growth of neurites up to 50% over a period of 24 hours.
“We discover more RNA targets that could promote the growth and regeneration of neurites,” said Mengting Han, a postdoctoral scholar in the QI laboratory and the main author of the newspaper.
“We have added a new tool to the CRISPR toolbox, using it to control the location of the RNA inside the cell. This has never been done before and, above all, it opens up new therapeutic directions to treat neurodegenerative diseases.”
Sure and more efficient RNA medicine
Researchers use CRISPR-TO to filter additional RNA molecules to determine which will be the most effective in repairing wounded neurons in the brain of the mouse, as well as in human neurons.
“We are at the beginning to understand how the spatial organization of RNA benefits the repair of the brain,” said Qi.
“We hope that our technology will help people understand which RNAs will be the greatest players for better therapies.”
Currently, researchers use CRISPR -TO to move endogenous RNA – RNA molecules which are naturally produced in the cell. But it could also be used to provide precise control over RNA medications, which makes them both safer and more effective, I said.
“This potential excites us enormously,” said Qi.
“It is not enough for a molecule to be simply in the cell. We need it to be in the right place at the right time. With our precise and programmable technology, you can target any RNA in any type of cell and bring it to the site of need in the body.”
Funding: This work was funded by the National Science Foundation, the National Institutes of Health, the National Center for Research Resources, the Stanford School of Medicine of the Postdoctoral Stock Exchange of the Stanford School of Medicine and the Postdoctoral Stock Exchange of the American Heart Association.
About this new CRISPR and research in neuroscience
Author: Chloé Dionisio
Source: Stanford
Contact: Chloé Dionisio – Stanford
Picture: The image is credited with Neuroscience News
Original search: Open access.
“Clonal tracing with somatic epimutations reveals the dynamics of blood aging” by Stanley Qi et al. Nature
Abstract
Clonal tracing with somatic epimutations reveals the dynamics of blood aging
The current approaches used to follow the stem cell clones by differentiation require genetic engineering or relying on clear sommatic DNA variants, which limits their broad application.
Here, we discover that the methylation of DNA of a subset of CPG sites reflects cell differentiation, while another subset undergoes stochastic epimstations and can serve as digital bar codes of clonal identity.
We demonstrate that the single target profiling of DNA methylation cells to a single CPG resolution can accurately extract the two layers of information.
To this end, we are developing Epi-Clone, a large-scale transgene-free line tracing method. Applied to the hematopoiesis of mouse and human, we capture hundreds of clonal differentiation trajectories through dozens of individuals and 230,358 unique cells.
In the aging of the mouse, we demonstrate that the myeloid bias and the low flow of old hematopoietic stem cells are limited to a small number of widened clones, while many functional type clones persist in old age.
In human aging, clones with and without mutations known to the driver of clonal hematopoïes are part of a spectrum of clonal expansions linked to age which have similar lines of line.
Epi-clone allows a precise monocellular line layout without transgene on state landscapes of large-scale hematopoietic cells.
