AUG 22, 2021 7:18 AM PDT

A Natural Protein to 'SEND' Gene Editing Cargo to Cells

WRITTEN BY: Carmen Leitch

One of the most difficult aspects of gene therapy might be ensuring that it gets into the right cells safely so it can have a therapeutic effect. Researchers have now created a new way to deliver various types of RNA cargo to cells, which utilizes one of the human body's natural proteins to create particles that can bind to RNA. This approach, called SEND, may help reduce any immune response that would be mounted against a gene therapy. The work has been reported in Science.

Current delivery systems are not efficient, may integrate their cargo improperly, and can cause serious immune reactions. “The biomedical community has been developing powerful molecular therapeutics, but delivering them to cells in a precise and efficient way is challenging,” said senior study author Feng Zhang, Ph.D., a core institute member at the Broad Institute, among many other appointments. “SEND has the potential to overcome these challenges.”

The new SEND technique (Selective Endogenous eNcapsidation for cellular Delivery) takes advantage of a natural protein encoded in the human genome called PEG10. This protein can bind to RNA and will typically form a capsule around RNA molecules, protecting them from degradation. This human protein comes from a retrotransposon. Millions of years ago, this genetic element inserted itself into the genome of human ancestors.

The body has gradually worked proteins that come from retrotransposons into various cellular processes. Zhang's team knew that these proteins can bind and package different molecules, so they began to study them as delivery systems.

PEG10 was selected as a good target; it can apparently be used to package therapeutic RNA molecules and deliver them to cells. In this study, the researchers showed that it was possible to use PEG10 to package the components for the CRISPR-Cas9 gene-editing system and send them into cells. When the approach was tested, it resulted in gene edits.

Image credit: Max Pixel

In this study, the investigators found the sequences in the mRNA of PEG10 that allow PEG10 to recognize and package its own mRNA (which it does normally). Then they engineered PEG10's untranslated regions to add various RNA molecules that would also be identified and packaged by PEG10. The resulting PEG10 capsules were also adorned with proteins called fusogens that help cells fuse together. The fusogens are meant to be used to target specific types of cells.

The researchers noted that PEG10 isn't the only protein that can do this, and they are also intrigued by what the normal function of these proteins may be.

“That's what’s so exciting,” said first study author Michael Segel, Ph.D., a postdoctoral researcher in the Zhang lab.“This study shows that there are probably other RNA transfer systems in the human body that can also be harnessed for therapeutic purposes."

“By mixing and matching different components in the SEND system, we believe that it will provide a modular platform for developing therapeutics for different diseases,” said Zhang.

This work has a long way to go before it could be used in a clinic; the next step is to test the technology in animals.

“We’re excited to keep pushing this approach forward,” Zhang added.

Sources: Massachusetts Institute of Technology (MIT), Science

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 09, 2021
Genetics & Genomics
DNA in the Nucleus Observed In a Surprising Formation
SEP 09, 2021
DNA in the Nucleus Observed In a Surprising Formation
In diagrams of cells, DNA is usually shown as a mass in the cell's nucleus, like a bowl of ramen noodles. But researcher ...
SEP 21, 2021
Genetics & Genomics
Skin Condition Linked to Sex Hormone Gene
SEP 21, 2021
Skin Condition Linked to Sex Hormone Gene
Eczema is a chronic, dry skin condition that affects millions of people. A form of the disorder called atopic dermatitis ...
SEP 26, 2021
Genetics & Genomics
A Better Gene Therapy Delivery System for Treating Muscle Diseases
SEP 26, 2021
A Better Gene Therapy Delivery System for Treating Muscle Diseases
Muscle diseases that have a genetic basis can cause muscles to waste away, and may lead to a premature death. There aren ...
OCT 04, 2021
Genetics & Genomics
Zaki syndrome - Pediatric Disorder & Potential Treatment ID'ed
OCT 04, 2021
Zaki syndrome - Pediatric Disorder & Potential Treatment ID'ed
Since it's become quick and relatively inexpensive to sequence a human genome, researchers have gained unprecedented and ...
OCT 05, 2021
Genetics & Genomics
Genetic Mutations May Not be Related to the Aging Process
OCT 05, 2021
Genetic Mutations May Not be Related to the Aging Process
As our body ages, cells have to divide to replenish those that become worn out or damaged. Most cells also carry the gen ...
OCT 10, 2021
Genetics & Genomics
Who Were the Etruscans? A Genetic Study Provides Some Answers
OCT 10, 2021
Who Were the Etruscans? A Genetic Study Provides Some Answers
The Etruscans lived in what is now Italy from about 800 BCE to the first century CE. Their language is now gone...
Loading Comments...