CRISPR Editing RNA? YES!

Written by Dr. Jonathan Peterson, Updated on February 7th, 2024, Published on September 5th, 2023

Reading Time: 5 minutes
()

The genetic altering technology called CRISPR has been advancing at a head-spinning, blistering pace. Recently it has evolved from a gene editor to adding a gene, editing multiple genes, shutting down harmful genes, changing and replacing single DNA letters, and even permanently altering the genetic information of an entire species.

But wait! There’s more!

Until recently, CRISPR has focused on DNA. However, instead of targeting DNA, researchers at MIT reprocessed CRISPR to edit single letters in RNA, the messengers that transport DNA information to the protein-building parts of the cell. Without RNA, most of DNA’s coding is meaningless: it’s like writing pages of software code, only unable to assemble it into an implementable program.

The research is led by Dr. Feng Zhang, a pioneer in recognizing CRISPR’s powerful editing abilities in mammalian cells. The current tool, called RESCUE, builds on Zhan’s prior attempt at using CRISPR to swap one RNA letter for another. That effort was commended and hailed as a “tour de force” by his fellow experts.

The difference now is that the editing is not limited to one gene. RESCUE can swap two letter pairs simultaneously, doubling the number of disease-causing mutations translated by RNA that can be checkmated. Also, the tool can change how molecules in our cells communicate information, ramping up—or temporarily blocking—the delicate “phone lines” that order cancer cells to grow or neurons to die from Alzheimer’s and other diseases.

Zhang stated, “To treat the diversity of genetic changes that cause disease, we need an array of precise technologies to choose from…we were able to fill a critical gap in the toolbox.”

RNA: Biomedicine’s Frontier

Zhang’s results are promising, but they are not the entire story. Let's see why scientists focus on RNA to grasp the big picture.

Consider RNA as a summary version of DNA. When a gene sends its message, it orders a crew of middlemen to quickly construct short, clover-leaf-shaped RNA strands containing all the “coding” information in a gene to make a protein.

Like DNA, RNA also has four letters—A, G, C, and U- similar to DNA’s T—that bind precisely with DNA. Three-letter combinations in RNA become a

dictionary that encodes different proteins; occasionally, it means “stop.” A total of 64 combinations of RNA triads create 20 different proteins that result in a second type of life’s base code.

RNA skyrocketed into prominence as a way to control gene expression nearly two decades ago, and in 2018, the FDA approved the first RNA-targeting gene-silencing drug. Despite the exploding popularity of DNA-focused CRISPR, however, targeting RNA remained a goal for three reasons.

First, it’s a no-commitment gene therapy option. Since RNA quickly regenerates, any errors in editing will disappear within a few hours, allowing scientists to discover another alternative rapidly.

Second, it achieves the same result as genome editing without added risk. Without editing the genome, which is risky, there’s no chance of causing permanent cancerous mutations or other severe side effects.

Third, targeting RNA can modify critical areas of a protein that are essential to its function. Proteins communicate with each other by adding—or deleting—specific chemical groups. It’s like either putting up or removing a “do not disturb” sign on your hotel room door; the cell’s staff will know whether or not to continue with their tasks.

Here’s why this is so significant.

Life depends on these signs: Should a brain cell die after a stroke? Should neurons accumulate protein clumps that trigger neurodegeneration? Should a cancer cell keep dividing? These chemical signals are a mother lode for treating all sorts of diseases. RNA-editing CRISPR is a simple, sturdy, and effective way to open them up for intervention.

In 2017, Zhang’s team uncovered the first CRISPR alternative that snips RNA into small bits, simultaneously destroying any carried genetic information in the molecules. Shortly thereafter, they developed the first RNA base-editing tool: REPAIR, a CRISPR variant that precisely changes the letter “A” to an artificial form of “G.”

A G-to-A mutation is expected in humans and appears in several health afflictions like epilepsy, Parkinson’s disease, and Duchenne muscular dystrophy. The new tool adjusts those mutations into benign forms without touching letters near the troubled area.

To build REPAIR, the team strung two parts together like a molecular buddy pro wrestling tag team. One is Cas13, a CRISPR family “scissor” protein that likes to cut RNA instead of DNA. The team created a neutered version that stripped the protein of its cutting ability but maintained its capability to grasp specific RNA sequences.

They then chemically linked the Cas13 mutant with ADAR2, a protein word processor that forces A to I. Together, the deactivated Cas13 tracks a target sequence in RNA, and ADAR2 swaps the letters.

The new system RESCUE uses REPAIR as its template. By analyzing the structure of ADAR2, the team made a few educated guesses to gradually change its activity so that the protein learns to turn “C” to “U” in an RNA molecule. Using a directed evolution procedure, they screened 16 rounds of RESCUE constructs in yeast cells until they found one with up to 80 percent editing efficiency.

A test with 24 clinically relevant mutant synthetic RNAs found editing proficiencies around 40 percent (some going as low as single digits). Further optimization decreased off-target hits to around 100 without disturbing on-target abilities. The team found that cultured human cells could efficiently alter the cell’s “do not disturb” molecular signs using RESCUE.

In one experiment, the team increased cell growth, similar to the process seen in prostate and other cancers. Another fascinating target is APOE2, a rare gene that lowers the risk of Alzheimer’s. Theoretically, RESCUE could alter the RNA transcripts to resemble the more brain-protective version, thus possibly helping at-risk individuals without editing their genetic profile.

RESCUE combines the top traits of RNA editing with the strength and resources of CRISPR, merging two of biomedicine’s most exciting approaches into a single tool. Compared to DNA-targeting CRISPR, it could finally put “undruggable” molecular targets within reach.

Now the bad news. RESCUE’s efficacy and specificity need years of more tinkering to be ready for clinical use. Since RNA regenerates, the editing effects are temporary, which could become problematic if counteracting a lifelong genetic disease.

But to some, that’s a feature, not a bug—it makes the tool useful for temporary conditions such as inflammation, stroke, or infectious diseases that only need brief treatments.

Applications of the CRISPR system to RNA are heating up,” said Dr. Gene Yao at UCSD, who funded a startup that uses CRISPR to target and slice up RNA for incurable conditions such as Huntington’s disease. His prior efforts constructed Cas9 variants that ignored DNA while destroying toxic RNA buildup to halt the progression of neurodegeneration.

RNA targeting has many advantages, and I think this will grow much more because there are many more things you can do to RNA than DNA,” said Yeo.

Reference

https://pubmed.ncbi.nlm.nih.gov/29070703/

Contact Us For HGH And Sermorelin Injection Treatment

Name (*)
Email (*)
Phone (*)
Select A Program (*)
Select US State (*)
Select Age (30+ only)

low testosterone symptoms mayo clinic consultant

Related Posts
nurse preparing businesswoman for blood test in hospital
growth hormone is hgh chart.webp
injections for sale united states hgh chart.webp

List of USA state clinics - click a flag below for blood testing clinics.

alabama clinics
Alabama Hormone Blood Analysis
alaska clinics
Alaska Hormone Blood Analysis
arizona clinics
Arizona Hormone Blood Analysis
arkansas clinics
Arkansas Hormone Blood Analysis
california clinics
California Hormone Blood Analysis
colorado clinics
Colorado Hormone Blood Analysis
connecticut clinics
Connecticut Hormone Blood Analysis
delaware clinics
Delaware Hormone Blood Analysis
florida clinics
Florida Hormone Blood Analysis
georgia clinics
Georgia Hormone Blood Analysis
hawaii clinics
Hawaii Hormone Blood Analysis
idaho clinics
Idaho Hormone Blood Analysis
illinois clinics
Illinois Hormone Blood Analysis
indiana clinics
Indiana Hormone Blood Analysis
iowa clinics
Iowa Hormone Blood Analysis
kansas clinics
Kansas Hormone Blood Analysis
kentucky clinics
Kentucky Hormone Blood Analysis
louisiana clinics
Louisiana Hormone Blood Analysis
maine clinics
Maine Hormone Blood Analysis
maryland clinics
Maryland Hormone Blood Analysis
massachusetts clinics
Massachusetts Hormone Blood Analysis
michigan clinics
Michigan Hormone Blood Analysis
minnesota clinics
Minnesota Hormone Blood Analysis
mississippi clinics
Mississippi Hormone Blood Analysis
missouri clinics
Missouri Hormone Blood Analysis
montana clinics
Montana Hormone Blood Analysis
nebraska clinics
Nebraska Hormone Blood Analysis
nevada clinics
Nevada Hormone Blood Analysis
new hampshire clinics
New Hampshire Hormone Blood Analysis
new jersey clinics
New Jersey Hormone Blood Analysis
new mexico clinics
New Mexico Hormone Blood Analysis
new york clinics
New York Hormone Blood Analysis
north carolina clinics
North Carolina Hormone Blood Analysis
ohio clinics
Ohio Hormone Blood Analysis
oklahoma clinics
Oklahoma Hormone Blood Analysis
oregon clinics
Oregon Hormone Blood Analysis
pennsylvania clinics
Pennsylvania Hormone Blood Analysis
rhode island clinics
Rhode Island Hormone Blood Analysis
south carolina clinics
South Carolina Hormone Blood Analysis
south dakota clinics
South Dakota Hormone Blood Analysis
tennessee clinics
Tennessee Hormone Blood Analysis
texas clinics
Texas Hormone Blood Analysis
utah clinics
Utah Hormone Blood Analysis
vermont clinics
Vermont Hormone Blood Analysis
virginia clinics
Virginia Hormone Blood Analysis
washington clinics
Washington Hormone Blood Analysis
washington d.c clinics
Washington, D.C. Hormone Blood Analysis
west virginia clinics
West Virginia Hormone Blood Analysis
wisconsin clinics
Wisconsin Hormone Blood Analysis
wyoming clinics
Wyoming Hormone Blood Analysis

How useful was this post?

Click on a thumb to rate it!

Average rating / 5. Vote count:

No votes so far! Be the first to rate this post.

Word Count: 1183