How Jumping Genes and RNA Bridges Promise to Shake Up Biomedicine

In 1948, a groundbreaking discovery was made by Barbara McClintock, a scientist working on the genetics of maize plants. She found that some genes, known as mobile elements or transposons, could move around within the genome, challenging the prevailing concept that genes were stable and arranged in an orderly manner on the chromosome. This revolutionary finding led to a deeper understanding of genetics and the role of transposons in enabling nature’s diversity.

Transposons, also nicknamed “jumping genes,” have the ability to influence gene expression by turning genes “on” or “off” using various epigenetic mechanisms. They are considered the tools of evolution, as they can rearrange the genome and introduce changes. Interestingly, more than 45% of the human genome consists of transposable elements, which can create diversity but also lead to diseases.

Researchers have been working to resurrect inactive transposons from animal genomes, hoping to use them in biomedical applications like genetic correction and gene therapy. For instance, a transposon called “sleeping beauty” was reprogrammed to work in human cells, and similar synthetic transposons could potentially be used to turn off problem genes or over-express desirable characteristics.

Recently, researchers at the University of California, Berkeley, and the Arc Institute published a paper describing a new RNA-guided gene editing system. This tool uses a bridge RNA molecule to edit DNA, allowing for the independent programming of target and donor DNA sequences. The study reported a high insertion efficiency and specificity in Escherichia coli bacteria.

In a separate paper, researchers from the University of Tokyo studied the structural and molecular mechanisms of genome modification guided by bridge RNA. They found that the IS110 transposons work as a dimer, binding to target and donor DNA sequences, and can facilitate the addition, deletion, or inversion of DNA sequences of any length.

This alternative form of genome-editing has many advantages over CRISPR-mediated editing, including the ability to make clean cuts and insert desirable genetic cargo. The technique has the potential to revolutionize synthetic biology, allowing for the insertion or removal of entire sets of genes from organisms. It can also be used to treat a wide variety of genetic diseases, including chromosomal inversions or deletions.

As McClintock said in her Nobel Prize lecture, “Unquestionably we will emerge from this revolutionary period with modified views of components of cells and how they operate, but only, however, to await the emergence of the next revolutionary phase that again will bring startling changes in concepts.” The discovery of jumping genes and RNA bridges promises to shake up biomedicine, offering new possibilities for genetic correction, gene therapy, and synthetic biology.

Historical Context:

The discovery of jumping genes, also known as transposons, by Barbara McClintock in 1948 was a groundbreaking finding that challenged the prevailing concept of gene stability and arrangement on chromosomes. This discovery led to a deeper understanding of genetics and the role of transposons in enabling nature’s diversity. Since then, researchers have been working to understand and harness the power of transposons for biomedical applications.

The concept of RNA-guided gene editing has been around for several years, with the CRISPR-Cas9 system being the most well-known example. However, the recent discovery of RNA bridges and their ability to edit DNA independently of CRISPR has opened up new possibilities for genome editing.

Summary in Bullet Points:

• Jumping genes, or transposons, are mobile elements that can move around within the genome, influencing gene expression and enabling evolution. • Transposons make up over 45% of the human genome and can create diversity but also lead to diseases. • Researchers have been working to resurrect inactive transposons from animal genomes for biomedical applications like genetic correction and gene therapy. • A new RNA-guided gene editing system uses a bridge RNA molecule to edit DNA, allowing for independent programming of target and donor DNA sequences. • The system has been shown to have high insertion efficiency and specificity in Escherichia coli bacteria. • The IS110 transposons work as a dimer, binding to target and donor DNA sequences, and can facilitate the addition, deletion, or inversion of DNA sequences of any length. • This alternative form of genome-editing has many advantages over CRISPR-mediated editing, including the ability to make clean cuts and insert desirable genetic cargo. • The technique has the potential to revolutionize synthetic biology, allowing for the insertion or removal of entire sets of genes from organisms. • It can also be used to treat a wide variety of genetic diseases, including chromosomal inversions or deletions. • The discovery of jumping genes and RNA bridges promises to shake up biomedicine, offering new possibilities for genetic correction, gene therapy, and synthetic biology.