The Little Warrior Foundation Awards $528,728 Grant to Dr. Mats Ljungman for Breakthrough Ewing Sarcoma Gene-Editing Therapy

Funding will support development of KLIPP, a pioneering CRISPR-based treatment at University of Michigan designed to precisely target and destroy Ewing sarcoma cancer cells.

Ever since Drs. Jennifer Doudna and Emmanuelle Charpentier developed CRISPR-Cas9, the Nobel Prize-winning “genetic scissors” capable of cutting DNA, a powerful “what if?” question emerged.

Rather than trying to inhibit, degrade, or attack Ewing sarcoma tumor cells through other  therapeutic approaches, what if one could directly cut the genetic fusion at its DNA core, rendering the cancer-driving program incapable of functioning? 

The fusion gene driving Ewing sarcoma (most commonly EWS::FLI1) is an ideal target for this strategy because it is a non-hereditary mutation found only in tumor cells, allowing for highly selective targeting.

But beyond the scientific fascination and endless “what if” moments, LWF has also been closely following the regulatory and safety hurdles required to bring gene-editing therapies into the clinic. Would the FDA ever allow this gene-editing technology to be unleashed in human, let alone kids?

One by one, the dominos have started to fall into place.

A major milestone was reported in late 2023 with the first approved CRISPR-based therapy for Sickle Cell Disease. In that approach, researchers removed cells from a patient, edited those cells ex vivo using CRISPR technology, and then reinfused the corrected cells back into the same patient - demonstrating that gene-editing could have transformative therapeutic potential for rare diseases

Then, in 2025, another watershed moment arrived. Baby KJ, suffering from a rare and life-threatening metabolic disorder caused by a liver enzyme deficiency, received an experimental in vivo CRISPR-Cas9 treatment designed to directly correct the underlying genetic mutation inside his body. After multiple infusions, the therapy showed encouraging early clinical improvement and marked a remarkable first step toward demonstrating that targeted gene editing could potentially be both feasible and safe in pediatric patients!

And lo and behold, after carefully evaluating several CRISPR-based programs alongside our expert Medical Advisory Board, LWF found a trailblazing researcher pursuing fusion-driven cancers with preliminary proof-of-concept data already targeting EWS::FLI1 itself!

Piero Spada, Co-Founder of Little Warrior Foundation (left) , with Michael Casuas from CureMEC (Center) and Mats Ljungman, MD (right) at the American Association of Cancer Research (AACR) Fusion-Positive Cancer Conference 2026.

Dr. Mats Ljungman and his laboratory at the University of Michigan have developed KLIPP (the Swedish word for “cut”), a next-generation CRISPR-based therapeutic platform designed to target cancer-specific structural variant junctions (gene fusions).

KLIPP utilizes guide RNAs that bind to precise DNA sequences on both sides of the fusion breakpoint. Only when both guide RNAs bind in close proximity is the Fok1 enzyme activated, enabling highly selective cutting of the cancer-driving fusion DNA. Without this genetic blueprint intact, the corresponding oncogenic protein can no longer be produced.

For more information on this novel approach, Dr. Ljungman and his team have created an outstanding animated video that walks through this science and vision in a highly accessible manner (if a picture is worth a thousand words, an animated video must be worth a lot more).

This funding from LWF will propel the laboratory forward by supporting the development of a weaponized lipid nanoparticle delivery system to more efficiently deliver KLIPP to tumor cells, followed by validation of this therapeutic strategy in both in vitro and in vivo Ewing sarcoma models.

While many important questions still remain, including efficient delivery throughout the body, the therapeutic vision is crystal clear: KLIPP places the EWS::FLI1 fusion directly in its crosshairs.

And for that, we remain deeply optimistic about what may one day be possible for patients and families facing Ewing sarcoma - Swords up!

This grant was partially funded by a $24,097 gift from Potawatomi Casino Hotel’s Heart of Canal Street program in honor of Aidan Onopa and his family.