Editor’s note: BioPharma Dive, as part of its newly launched Emerging Biotech Weekly, is taking a closer look at competitive areas of startup activity. We aim to give an overview of the companies developing a new technology and what their goals are. This, on epigenetic editing, is our first.

A decade has passed since the first scientific paper emerged describing a new way to alter DNA with a bacterial defense system known as CRISPR. Two of the authors, researchers Jennifer Doudna and Emmanuelle Charpentier, are now Nobel laureates, and the gene editing technology they pioneered birthed a group of biotechnology companies now testing it as a way to potentially cure a range of inherited disorders.

But innovation happens fast in the biotech industry. Even before the first CRISPR drug developers complete their clinical trials, new startup companies aiming to surpass them are following quickly in their footsteps. “Base” and “prime” editing, touted as more precise tools, have attracted sizable investment. So has another approach targeting the RNA molecules that help turn DNA into proteins. All represent ways to broaden the reach of genetic medicine.

The latest twist may come from a field of research, known as epigenetics, that’s intrigued drug researchers for years. Here’s where things stand:

What is epigenetic editing, and how does it work?

Epigenetics studies the proteins and chemicals that turn genes on and off, without altering the underlying DNA.

For years, scientists and drugmakers have tried to find the right molecular switches that cause a gene to make a protein, and use that information to treat disease. For instance, a chemically linked configuration of carbon and hydrogen atoms — known as a methyl group — can bind to DNA and change how, or whether, certain genes are “read” by specific proteins. Chemical changes to proteins called histones that hold onto DNA can also alter gene expression.

So far, that knowledge has led to limited drug development successes in the form of a few chemical-based cancer medicines. Merck & Co.’s lymphoma drug Zolinza targets a protein that affects the chemical makeup of histones. Epizyme’s soft tissue cancer drug Tazverik, meanwhile, blocks an enzyme involved in gene expression.

But in many cases it’s been difficult to determine which switches control what genes, or how to get to them without causing other problems. Using new computing tools and advances in genomic research, a number of biotech companies pushed ahead with research, and are now joined by others seeking to use CRISPR-based tools. Their idea is to use CRISPR components to turn genes on or off, or to alter the expression of several at a time without cutting into or changing DNA.

What advantage would epigenetic editing offer over existing technologies?

The first iteration of CRISPR is often likened to “molecular scissors.” But, relative to the genetic changes researchers might want to make, the scissors’ blades are somewhat blunt. By cutting through DNA’s double-stranded helix, CRISPR can make accidental, off-target edits, which could have real health risks, such as damage to genes that suppress cancer.

Newer approaches are designed to make more pinpoint changes. Base editing can alter single nucleotides, or “letters,” in a gene, but only for certain combinations. Prime editing is more flexible still, capable of swapping any DNA letters as well as editing out specific sequences of nucleotides.

However, both approaches involve breaking or rewriting DNA in one way or another. Epigenetic alterations don’t, meaning they might be reversible and could help developers to more subtly dial up or down gene expression. Proponents of the approach believe these capabilities may allow gene editing to be used for a wider range of diseases, including complex conditions beyond the reach of existing technologies. But that hasn’t yet been proven.

Which companies are working on it, and who is backing them?

Since last November, three biotechs planning to edit the epigenome have launched with significant funding.

Chroma Medicine was seeded by Atlas Venture and Newpath Partners and is based on the work of MIT scientist Jonathan Weissman, who co-founded the company along with gene editing specialists David Liu and Keith Joung.

Tune Therapeutics, co-founded by Duke University researcher Charlie Gersbach and another gene editing pioneer at UC Berkeley, Fyodor Urnov, is backed by New Enterprise Associates and led by the former CEO of Precision Biosciences.

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