A breakthrough technique in gene therapy involving the use of retrotransposons from birds has been developed by researchers at the University of California, Berkeley. The method, known as Precise RNA-mediated INsertion of Transgenes (PRINT), leverages retrotransposons to insert entire genes into a specific "safe harbor" in the human genome without disrupting essential genes or increasing the risk of cancer.

Published on Feb. 20 in the journal Nature Biotechnology, the PRINT technique utilizes a common retroelement protein called R2 protein to efficiently insert genes into the genome. By targeting an area with hundreds of identical gene copies, the transgene can be inserted without affecting vital functions. This method differs from CRISPR-Cas9 gene editing, which primarily focuses on disabling or fixing genes with mutations.

The study, led by Kathleen Collins, a professor of molecular and cell biology at UC Berkeley, discovered that birds like the zebra finch and white-throated sparrow possess retrotransposons that are particularly effective at gene insertion. These retrotransposons were found to target the ribosomal RNA encoding region of the human genome, providing a safe and efficient environment for transgene insertion.

In experiments using cultured human cells, researchers successfully inserted a fluorescent protein gene into the genome using the PRINT technique. The inserted transgene integrated into the rDNA regions without disrupting normal gene expression. The ribosomal DNA regions were chosen for insertion due to their regulated transcription and enhanced DNA repair capabilities within the nucleolus.

While further research is needed to fully understand the mechanism of action of R2 protein and its impact on rDNA transcription, the initial results are promising. The researchers are now working on optimizing the technique for better efficiency in human cells and tissues.

The PRINT gene therapy technique offers a new approach to treating hereditary diseases by supplementing functional genes into the genome, rather than reversing mutations. With the potential to address a variety of genetic mutations that cause loss-of-function diseases, this method could revolutionize gene therapy for conditions like cystic fibrosis and hemophilia.

Overall, the PRINT technique represents a significant advancement in the field of gene therapy, providing a safe and effective means of inserting whole genes into the human genome for therapeutic purposes.