Doing the Moonwalk

Our newest investment: AI-driven epigenetic editing for novel modes of precision medicine.

Moonwalk’s molecular tools are like CRISPR for methylation tags, and not the DNA itself.
Genes are the firmware, epigenetics is the software. Moonwalk.Bio

Excerpts from today’s news
• From Genetic Engineering & Biotech News:

“The company has an impressive leadership team with deep expertise in areas such as epigenetic editing and clinical product development. In addition to Aravanis, Moonwalk’s co-founders include Arash Jamshidi, PhD, and Justin Valley, PhD, as well as scientific co-founder Feng Zhang, PhD, [pioneer of CRISPR editing]. Since leaving his role as Illumina’s chief technology officer last year, Aravanis has spent the bulk of his time working on building Moonwalk.

Moonwalk plans to develop a pipeline of treatments capable of using the cells’ natural regulation system to accurately and permanently control multiple genes in a single step without making changes to the primary DNA sequence. This is an important point and one that is highlighted by several companies that are trying to reprogram diseased cells by targeting the epigenetic code.

Activating or suppressing genes by methylating or demethylating particular targets rather than snipping and inserting DNA sidesteps some of the inherent risks of editing genes directly including potential structural changes or unintended insertions. An added benefit is the durability of epigenetic changes. The data suggests that modifications to methylation do stay in place and those changes are successfully transmitted to daughter cells even after multiple cell divisions.

‘There’s been a lot of evidence mounting over the years about the importance of the epigenome in health and disease. And also obviously cells change a lot as we age and as they develop pathologies. And that’s reflected in the epigenome,’ Aravanis said. ‘It’s a very appealing concept to be able to kind of see root level changes in the epigenome and then have a technology to modify it and then develop therapeutics based on that.’

Moonwalk claims to be the first company to couple an epigenetic discovery platform with precise engineering. Its proprietary technology has two key components. A so-called read component is designed to capture methylation information from the entire genome—about 28 million sites. It gives the company insights into the methylation present in both healthy and diseased states, allowing it to make predictions about complex methylation patterns as well as identify which are the best targets to hit.

The rubber meets the road in the second component of the company’s platform. This is where the company uses editing technology designed by Zhang, the company’s scientific co-founder, to modify methylation states in the genome. In addition to his work on CRISPR, Zhang is perhaps ‘one of the earliest inventors of this concept of modifying the epigenome directly,’ Aravanis noted, making him a natural fit for the company.”

• From Longevity Tech:

“’While changes to the genome are irreversible, edits to the epigenome can be reprogrammed in different ways,’ said Moonwalk CEO Aravanis, who co-authored a recent paper in Nature describing a DNA methylation atlas of human cells. ‘Epigenetic changes determine whether genes are turned on or off, and can potentially reverse disease, broadening the therapeutic landscape to find potential cures previously thought impossible.’
Potential in age-related disease: Cellular reprogramming is a hot topic in longevity, and Aravanis told us that Moonwalk is studying its effect on the epigenome.

‘By converting transcription factor expression protocols into more precise epigenetic programs, it may be possible to achieve the benefits of programming or partial reprogramming, but with more specific control over cell state,’ he said. ‘For example, to gain the benefits of higher function without losing the somatic features of cells.’

When it comes to the company’s potential in targeting diseases of aging specifically, Aravanis told us that epigenetic alterations are “a hallmark of aging that strongly correlate with decline in cell function.”

‘There is increasing evidence that these alterations are causally related to loss of function,’ he said. ‘Moonwalk’s epigenome engineering platform can identify these epigenetics changes with unprecedented resolution, predict which targets may be causally related to the loss of function, and then reverse their methylation state, testing them as candidates to restore cell function.’”

• From the WSJ :

“Proponents say this new twist on genetic medicine, ‘epigenetic editing,’ promises to lead to treatments or cures for a variety of common medical scourges, such as cancer and chronic hepatitis B.

Epigenetic therapy attempts to tap nature’s method of regulating what a gene does, or its expression. Cells in various organs harbor the same genes. But a system of controlling which genes are turned on or off—epigenetics—determines whether a cell turns into a heart, brain or other type of cell.

South San Francisco, Calif.-based Moonwalk, which was founded in 2022 and operated quietly until recently, seeks to harness a form of epigenetic control that involves adding chemical tags, known as methyl groups, to DNA. Adding a methylation tag suppresses a gene, while removing one can allow it to be activated.

Bing Ren, director of the Center for Epigenomics at the University of California, San Diego, said he is optimistic the approach could be a breakthrough, partly because it could open new angles of attack on diseases.”