Article image

Birds inspire a safer method of editing human genes

Gone are the days when editing human genes was risky and dangerous. A new method called PRINT offers amazing accuracy and safety, making it a breakthrough in treating genetic diseases. The technique was developed by researchers at UC Berkeley, led by Professor Kathleen Collins. 

The RNA-based gene editing technique is a giant leap forward in medical technology, allowing us to target specific areas of our DNA with incredible accuracy.

Evolution of gene therapy

For years, scientists have been working on ways to deliver “good” genes to fix “bad” ones in people with diseases like genetic disorders, some cancers, and even infections.

At first, the experts used viruses to carry the genes, but there were risks like allergic reactions and even cancer. Then, a tool called CRISPR-Cas9 came along, letting them edit genes more precisely. But it could still make unexpected changes and damage the DNA. 

The new tool aims to bypass the existing challenges. “A CRISPR-Cas9-based approach can fix a mutant nucleotide or insert a little patch of DNA – sequence fixing. Or you can just knock out a gene function by site-specific mutagenesis,” said Professor Collins. 

“We’re not knocking out a gene function. We’re not fixing an endogenous gene mutation. We’re taking a complementary approach, which is to put into the genome an autonomously expressed gene that makes an active protein – to add back a functional gene as a deficit bypass.”

“It’s transgene supplementation instead of mutation reversal. To fix loss-of-function diseases that arise from a panoply of individual mutations of the same gene, this is great.”

Working of PRINT

Instead of inserting the genes randomly, like older methods, PRINT is a technique that uses special elements found in birds DNA called “retrotransposons.” The gene editing technique works in three phases.


First, tiny packages containing two RNA messages are delivered into the cells. One message tells the cell to build a retrotransposon called R2, acting like a special key.

The other message carries the blueprint for the new, helpful gene. This blueprint includes the gene itself and instructions for using it (regulatory elements).


The R2 protein, the key, recognizes and binds to specific “safe harbor” sites in the DNA. These are areas with multiple copies, so altering one won’t harm the cell. 

R2 acts like tiny scissors, carefully cutting open the DNA at the safe harbor site. Using the blueprint as a guide, R2 integrates the new “good” gene into the open space it created.


The blueprint’s regulatory elements tell the cell how to use the new gene. They act like switches, turning on the gene and instructing the cell to start producing the desired protein.

The body now produces the protein encoded by the new “good” gene, potentially addressing the disease or condition.

The selection of R2

The scientists were looking for a way to safely and accurately insert new genes into human cells for gene therapy. Their initial idea, using a different type of genetic element called LINE-1, seemed promising, but it turned out to be too complex and difficult to control.

Fortunately, previous research showed that genes inserted into specific regions of the genome called “ribosomal RNA genes” (rDNA) worked normally. These regions are repetitive and abundant, making them an attractive target for editing genes.

The scientists focused on an element called R2, which naturally inserts itself into rDNA in other animals, but not humans. They tested R2 from various creatures, like insects, birds, and even horseshoe crabs, searching for the best version for human cells.

“After chasing dozens of them, the real winners were from birds,” Professor Collins said, specifically zebra finches and white-throated sparrows. This R2 was highly specific to human rDNA and could insert larger pieces of DNA. Interestingly, this specificity likely originated from an ancient “ancestor” of R2 that existed in mammals but was later lost.

Successful results

Experiments confirmed that bird-derived R2 worked well. Scientists created a message and delivered it to human cells, instructing them to make both R2 and the desired new gene. Many cells successfully incorporated the new gene into their rDNA, and everything continued to function normally.

This careful selection of R2, based on both scientific understanding and experiments, is key to the innovative PRINT technique. By harnessing R2’s unique abilities, the UC Berkeley team has developed a precise, safe, and broadly applicable gene therapy approach, opening new doors in genetic medicine.

Promising technique 

PRINT offers a new way to deliver entire genes directly into the body, potentially treating more genetic disorders than ever before. Diseases caused by missing or faulty genes, like cystic fibrosis and hemophilia, could be corrected by adding back the missing piece.

While CRISPR-Cas9 is efficient at editing genes, it struggles with adding large chunks. PRINT fills this gap, allowing scientists to completely add new genes and work even better with CRISPR.

PRINT works by targeting specific spots in the genome, avoiding any disruption to important genes or potentially causing cancer. This is a big improvement over older methods that could have serious side effects.

Unlike other gene therapies, PRINT doesn’t need to be customized for each patient, making it simpler and faster to develop treatments for many people. This could save time, money, and bring relief to more patients sooner.

Future research

PRINT technology holds immense potential for treating diseases at the genetic level, but several key areas need further exploration to unlock its full potential. 

Firstly, a deeper understanding of how genes integrate into DNA after delivery is crucial to prevent unintended changes and ensure gene integrity. Additionally, optimizing the technique for longer genes, which currently pose a challenge, requires finding ways to deliver them intact and functional. 

Minimizing cellular reactions to the introduced RNA components is also essential for broader acceptance and improved integration efficiency. Understanding how long these delivered genes remain active in different disease contexts is vital for assessing the long-term efficacy and safety of PRINT-based therapies. 

Furthermore, expanding PRINT’s effectiveness beyond rapidly dividing cells holds promise for new treatment avenues. Refining the proteins involved in the process by leveraging protein engineering could significantly boost its overall efficiency. 

Finally, gaining a deeper understanding of the key molecule, EN, will allow for precise optimizations and broaden the applicability of PRINT technology. 

Hope for precision medicine

Such advancements in gene editing technology hold immense promise for revolutionizing the treatment of genetic diseases. Their capability extends beyond simply introducing new genes – they offer unparalleled precision in doing so. 

This opens the door to designing treatments that target the fundamental molecular cause of the disorder, rather than solely managing symptoms. 

Read more on the study in the journal Nature Biotechnology.

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates.


Check us out on EarthSnap, a free app brought to you by Eric Ralls and

News coming your way
The biggest news about our planet delivered to you each day