Coinciding with the historic approval of Vertex and CRISPR Therapeutics’ Casgevy as the first CRISPR-based therapeutic, epigenetic editing, which targets parts of the genetic code beyond the DNA itself, is having a moment. One company is already in the clinic, and two more are on pace to follow with therapies based on what some experts say is a safer alternative to gene editing.

According to a recent report by Precedence Research, the global epigenetics market is expected to hit $6.35 billion by 2032, an increase from $2.14 billion in 2023. In January, CRISPR luminary Feng Zhang launched Moonwalk Biosciences, which is making precision epigenetic medicines for complex diseases, and Novo Nordisk this year embarked on a research partnership with Omega Therapeutics to develop an epigenomic controller designed to enhance metabolic activity. Meanwhile, Gilead’s Kite has struck an alliance with Epic Bio to leverage that company’s epigenetic editing platform for next-generation cancer cell therapies.

Although it’s still early days for this technology, experts who spoke with BioSpace said they’re optimistic that epigenetic editing will enable more broadly applicable and potentially safer therapies. And they estimate they could hit the market by the end of the decade.

“We should be able to [have] an approved [epigenetic editing] drug within the next five years,” Charlie Gersbach, a professor of biomedical engineering at Duke University whose lab spawned epigenetic editing company Tune Therapeutics, told BioSpace.


Epigenetic Editing: A Safer Approach?

For the past decade, epigenetic editing has hovered on the sidelines as gene and cell therapy stole the spotlight. This was in part due to a limited understanding of the science, Gersbach said. When the human genome was first sequenced in 2003, he explained, “we knew very little about what the different parts were, how they were controlled, how it varied across cell types, disease [and] individuals.” But as researchers’ understanding of epigenetics has matured, they are now able to manipulate gene expression and protein levels without editing the DNA. This has led to efforts to develop this technology into therapeutics, Gersbach said.

Epigenetic editing therapies may also avoid the potential side effects of CRISPR-based approaches, said Dan Hart, head of technology development at Epic Bio, which is developing an epigenetic editing treatment for facioscapulohumeral muscular dystrophy (FSHD). During gene editing, unintended cuts in the DNA can lead to unwanted cell growth and cancer. “So then the pressure is on to find improvements and innovations, and now you see the shift to . . . what else can we do? Where else can we go?” Hart said.

Enter epigenetic editing, where it’s possible to achieve durable outcomes “without making any changes whatsoever to the underlying DNA sequence, so there’s no risk of any off-target—or even any on-target—permanent changes to the genome,” said Tune CEO Matt Kane.

Now, Omega is in Phase I/II clinical trials with OTX-2002 for liver cancer, and Tune is nearing the clinic with a first-in-class epigenetic silencer for hepatitis B (HBV). Kane anticipates filing a Clinical Trial Application around the middle of 2024 with the New Zealand Ministry of Health.

Meanwhile, Epic Bio plans to file an Investigational New Drug application for its FSHD candidate, EPI-321, during the first half of this year, CEO Amber Salzman told BioSpace. Hart added that the company hopes to have an approved product by 2028.


Ubiquitous Potential

While many gene-editing therapies are focused on fatal genetic diseases, epigenetic editing’s safety profile may enable the treatment of more common diseases. The fact that no underlying changes are made to the DNA sequence “offers some additional safety assurances for this approach compared to some others where the risk/benefit [ratio] needs to be maybe a little different before you would employ those technologies,” Kane told BioSpace.

Additionally, because most common diseases are not driven by genetic mutations, epigenetic editing may be a better fit. “Most of those diseases are driven from expression levels being at an unhealthy level,” Kane said. “That is something that a tool like epi[genetic] editing is uniquely well-suited to address.”

Another advantage is the potential of epigenetic editing to be mutation agnostic, Salzman noted. Epic Bio is also developing a treatment for Retinitis pigmentosa, a degenerative eye disease that can be caused by a lot of different mutations. “If you have to cut the mutation out, you’d have to have a specific product for each of those mutations,” Salzman explained. “But because we’re . . . just suppressing whatever the mutant protein is, we can have one therapy to cover all the mutations.” This can give a company a bigger market share, she said.

One area where Kane sees potential for epigenetic editing is in treating diseases of aging. “As we age, it’s almost always the epigenome that is driving these more aged and exhausted states in different tissues and cell types,” he explained.

Lei Stanley Qi, Epic Bio’s scientific founder, said that epigenetic editing is “inevitable” in genetic drug development. Just ten years ago, scientists were asking whether CRISPR-Cas9 could even work in human cells, Qi told BioSpace, and now, Casgevy is rolling out to patients with sickle cell disease and beta thalassemia.

“Medicine is going to be changing a lot in the future,” Qi said. “And that’s why we are really working hard, trying to make epigenetic editing also benefit people sooner than later.”


Successfully Delivering to the Right Target

As with gene editing and other types of gene therapy, Gersbach said the biggest challenge facing epigenetic editing is delivery. “Whether it’s a gene replacement, or a DNA editor or an epigenome editor, you still have to get it to the right cells and tissues, and that’s probably the biggest bottleneck for the whole field.”

Qi agreed, saying it is difficult to deliver the therapy to many disease sites and organs, particularly with lipid nanoparticles, whose larger cargo size is attractive to many companies but naturally gravitates mainly to the liver. Epic Bio’s initial programs are using adeno-associated virus vectors, which are more versatile, but have a smaller cargo capacity, “so it’s really challenging to design gene editors or epigenetic editors to be small enough to fit,” Qi explained. So, Epic Bio has developed smaller molecular machinery, ultimately shrinking the size of the molecules by more than 60% from where the field initially started.

Delivery issues could be a relevant factor as companies pick their initial targets—something Kane advised considering carefully. “We need to be really thoughtful about whether or not we’re going to be able to get a clear and convincing clinical readout initially with these programs so that we can really establish and validate this new approach clinically.”

Ultimately, Gersbach said that “while gene editing is really useful for certain things and gene therapy is useful for specific things, I believe strongly that epigenome editing [is] going to be more broadly useful for more diseases and more common diseases that affect more patients.”

Check out our AAV CDMO service to expedite your gene therapy research
About PackGene

PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.

Related News

Future Of Gamma Delta T Cell Therapies

Gamma delta T cell-based immunotherapies have emerged as a promising frontier in cancer treatment and beyond, building on the success of chimeric antigen receptor T-cell (CAR T cell) therapy and expanding on the potential of the immune system as a therapeutic...

read more

Related Services

Plasmids GMP Services

Multiple scales & grade of solutions of various kind of plasmids suitable for multiple treatments in a fast and cost effective way.

AAV GMP Services

Ranging from small-scale AAV production, to large-scale AAV cGMP manufacturing for animal studies.
aav icon

Technology Platforms

PackGene’s proprietary π-Alpha™ 293 AAV High-yield Platform increases AAV production by 3 to 8 times that of traditional platforms.