Gene Editing

Cutting-edge technologies to repair the underlying mutations that cause Rett.

There are several different types of gene editing technologies. Our programs use the highly efficient CRISPR-Cas system which consists of two key molecules. The first is an enzyme called Cas9 which acts as a pair of molecular scissors that can cut DNA at specific locations so that bits of DNA can then be added or removed. The second is a guide RNA that brings the Cas9 enzyme to the proper location in the genome.

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What it is

In contrast to gene replacement, which delivers healthy genes to compensate for mutated ones, gene editing uses genetic engineering technologies to insert, delete, or replace DNA.

Why it matters

Acting like molecular scissors, gene editing can target the precise location of the genetic error among the more than three billion base pairs in our genome. Importantly, gene editing avoids the potential of delivering too much of the “Rett gene.”

Status

RSRT is funding two programs in gene editing. Beam Therapeutics, a leading editing biotech, is tackling specific mutations while a collaboration of powerhouse labs at the University of Massachusetts Medical School seeks to edit a large section of the Rett gene where 97% of the mutations reside.

A Deeper Dive
into the Science

Genes are made up of specific nucleotide bases (A, T, C and G) which encode for amino acids. Every three bases code for a specific amino acid. The MECP2 gene has 1497 nucleotide bases (A,T,C,G) that code for the 498 amino acids in the MECP2 protein. Alterations in the MECP2 gene range from a single letter to large sections of the gene being deleted or inserted. (To learn more about the genetics of Rett Syndrome please visit our Genetics Primer.)

Beam Therapeutics is focused on editing point mutations — mutations caused by a single nucleotide base error. This approach, known as “base editing,” would require a novel therapeutic to be developed for each point mutation. Another group, led by Jonathan Watts at University of Massachusetts Medical School, is pursuing “exonic editing” in which a single therapeutic would replace all of the 1,435 nucleotides in exons 3 and 4 and thereby correct 97% of all known mutations that cause Rett Syndrome.

The technology is amazing and provides a unique opportunity to potentially do something very meaningful for Rett patients.

Giuseppe Chiaramella, PhD, President and Chief Scientific Officer
Beam Therapeutics

Beam Therapeutics

Beam Therapeutics is a leading gene editing biotech whose founders include three of the top scientists in the field: Keith Joung, designated as one of the most cited researchers in the world by Thomson Reuters; David Liu, named by Nature in 2017 as one of the top 10 researchers in the world; and Feng Zhang, one of the pioneers of the CRISPR gene editing field.

Beam is pioneering the use of a CRISPR technology called “base editing” to precisely and permanently correct specific nucleotide point mutations. This technology involves the creation of a single protein that combines the targeting ability of CRISPR with novel enzymes that are able to convert the mutated nucleotide base to the correct base.

The system is modular, so different components can be selected based on the mutation that needs repairing. If successful, base editing therapeutics would be a one-time procedure and would be delivered either via virus (as with gene replacement) or non-viral delivery technology.

This project brings to bear the expertise and resources of a leading gene editing company and an industry approach to research into a potentially novel class of therapeutics for Rett Syndrome.

University of Massachusetts
Medical School

Researchers Jonathan Watts, PhD, Erik Sontheimer, PhD, Scot Wolfe, PhD, and Anastasia Khvorova, PhD, are among the world’s leaders in knowledge of RNA chemistry. UMASS has played a historic role in this space for years; in 2006 Craig Mello was awarded the Nobel Prize for his work in RNA silencing.

UMASS, and this group in particular, also have expertise in the now universally-used DNA editing machinery, CRISPR-Cas9. Erik Sontheimer co-founded and launched one of the very first CRISPR companies, Intellia.

Using CRISPR-Cas9 the scientists seek to replace exons 3 and 4 at the DNA level to effectively correct 97% of all known mutations that cause Rett Syndrome. This is the DNA version of what Stuart Cobb is doing with RNA trans-splicing and we believe it’s important to pursue both the DNA and RNA options in parallel to ensure all possible therapeutic avenues are tested.

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A cure for Rett.
You want it.
We want it.

Great achievements happen when people stand up and say I’m in. I will be part of the solution!

Rett may be a rare disorder but together we are powerful.