Yale announces IV gene-editing technique
Scientists at Carnegie Mellon University and Yale University have developed nanoparticles that are safe to interact with living tissue for a treatment to repair a malfunctioning gene in live mice. Using Food and Drug Administration-approved nanoparticles and a peptide nucleic acid (PNA) molecule, scientists were able to create "DNA-PNA-DNA triplexes" on genes which caused blood disorder beta-thalassemia. The system had a 7% success rate compared to current methods, which have a success rate of 0.1%.

Researchers at Carnegie Mellon University and Yale University have developed a new, minimally invasive, gene-editing system that can be used to cure genetic blood disorders in live mice. As opposed to other gene-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and zinc-finger nucleases, this technology uses an IV treatment and does not mutate genes that weren’t meant to be mutated. This system uses peptide nucleic acids (PNAs), synthesized polymers comprised of a protein backbone with DNA and RNA nucleotides attached to it.

CRISPR has been hailed as the "most important innovation in the synthetic biology space in nearly 30 years" and the interest in it as measured with respect to patents, scientific publications, and government funding has skyrocketed since 2013, according to a Washington Post article.

However, CRISPR’s method of using the immune systems of bacteria to identify and modify certain DNA sequences at a specific site has its drawbacks. It uses DNA-cutting enzymes to cut open a slice of DNA and then change it. First, these enzymes cannot be inserted effectively into a living body, unlike PNAs. CRISPR involves taking the affected cells outside the body, treating them, and then placing them back into the affected region. Second, while treating the cells, the enzymes might affect cells with similar sequences and create sporadic, unwanted mutations.

In an official university press release, Danith Ly, a professor in the Department of Chemistry at Carnegie Mellon, explained, “We have developed a system that uses FDA-approved nanoparticles to deliver our PNA molecule along with a donor DNA to repair a malfunctioning gene in living mice. This has not been achieved with CRISPR."

The system developed by Carnegie Mellon and Yale overcomes both of these problems using PNAs. The system comprises of nanoparticles that are safe to interact with living tissue, which contain PNAs and donor DNA. PNAs are also synthesized nanoparticles that are basically the nucleobases of DNA and RNA attached to a protein backbone. This allows them to bind to the DNA in the affected region with high affinity, without actually cutting the DNA at the site. It simply opens up the double-stranded DNA and performs its function. The nano-particle delivery system that PNAs can be used with has been approved by the United States Food and Drug Administration and has been used successfully to treat neurodegenerative diseases in humans.

Ly and Raman Bahal, a former graduate student, together with Peter Galzer’s team from Yale University, created the nano-particles that contained the PNA which, on binding to the target site, created DNA-PNA-DNA triplexes after displacing a DNA strand. This triplex then creates a favorable environment for the donor’s DNA to bind to the faulty DNA site in the locality. This was tested on genes that cause beta-thalassemia, a blood disorder wherein the lack of hemoglobin in the body creates acute oxygen shortage throughout the body and induces fatigue, weakness, and other severe issues.

This resulted in increased hemoglobin levels for several months after treatment and a success rate of 7 percent in gene-editing. This is significantly higher than the current commonly used methods, which report a success rate of only 0.1 percent. In the press release, Ly, referring to the results, says “The effect may only be 7 percent, but that’s curative,” Ly said. “In the case of this particular disease model, you don’t need a lot of correction. You don’t need 100 percent to see the phenotype return to normal.”

The reports of this research were published in the journal Nature Communications.