Researchers from Shenzhen Bay Laboratory, Shenzhen Academy of Medical Sciences, Peking University Shenzhen Graduate School, and Shanghai Spinoin Biotechnology Co., Ltd. recently collaborated with Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine and obtained approval to conduct the world's first clinical trial using a non-viral vector full-length dystrophin (FL-dystrophin) gene therapy to treat Duchenne muscular dystrophy (DMD) .

This is also the first international clinical trial initiated by researchers (IIT) to introduce gene therapy drugs into humans using an extracellular vesicle delivery platform.

The project, titled " A novel mRNA platform based on engineered extracellular vesicles (EVs) to treat Duchenne muscular dystrophy ", aims to deliver FL-dystrophin mRNA through engineered extracellular vesicles, evaluate its safety, tolerability and preliminary efficacy in DMD patients, and provide patients with safer and more efficient gene therapy options.

01 Research background and scientific basis

Duchenne muscular dystrophy is a fatal genetic disease caused by a mutation in the dystrophin gene on the X chromosome, affecting 1 in every 3,500 male babies worldwide.1 Patients suffer progressive muscle weakness due to loss of muscle cell membrane stability, usually losing the ability to walk in adolescence and dying early from cardiopulmonary failure.

There is currently no cure for the disease. Although current therapies such as ASO or AAV vector gene therapy can partially restore dystrophin expression, they still face limitations:

1) Lack of universality to cure all mutation types;

2) A single dose of AAV may activate innate and adaptive immune responses and cause multiple organ failure, especially liver, heart, and lung damage, or even death from liver failure2 ;

3) Clinical cases of AAV treatment have shown that its toxicity is dose-dependent and closely related to the patient's baseline condition (such as liver disease) 3. In addition, on June 15, 2025, Elevidys, the only gene therapy drug approved by the US FDA for DMD, was withdrawn from the market due to multiple cases of AAV liver toxicity leading to patient deaths.

These events highlight the need to develop new safe non-viral therapeutic strategies to treat muscular dystrophy.

02 Advantages of mRNA therapy

The success of mRNA vaccines in combating the COVID-19 pandemic has drawn attention to mRNA therapeutics.

mRNA therapy refers to mRNA directly inducing the synthesis of target proteins in cells, which has the advantages of low toxicity and low immunogenicity compared to AAV therapy . In addition, mRNA therapy has good plasticity and can be used to compile any protein. Therefore, mRNA therapy can directly supplement the missing dystrophin in DMD patients, thereby restoring muscle fiber integrity and solving the difficult problems of loss of muscle regeneration ability and mitochondrial dysfunction.

Many clinical and preclinical studies have found that AAV has many defects as a carrier of gene drugs, such as liver toxicity, nerve and blood damage, renal failure caused by thrombotic microangiopathy, and death from acute liver failure. These adverse reactions limit the research and development of AAV therapy for the treatment of DMD, and there is an urgent need to innovate and develop safer and more effective treatment methods.

mRNA therapy can overcome the limitations of therapies such as ASO and AAV in the treatment of DMD, but its true clinical application requires a safe and effective delivery vector .

03 Innovative EV mRNA Platform

In order to break through this bottleneck, the research team took a unique approach and turned their attention to engineered extracellular vesicles (EVs), a natural nanoscale delivery vehicle.

As a tiny vesicle secreted by cells, engineered EVs have excellent biocompatibility and low immunogenicity. They can easily cross multiple biological barriers and accurately deliver the genetic material they carry to target cells.

- mediated mRNA delivery strategies4,5 .

The EV mRNA platform breaks through technical bottlenecks through the following innovative designs:

1) Full-length protein supplementation : FL-dystrophin mRNA is delivered through EV to directly repair gene defects, breaking the limitations of traditional therapies due to the incomplete function of truncated proteins;

2) Non-viral delivery system : Unlike AAV vectors that can cause immunogenicity and cardiotoxicity, there is no risk of viral toxicity. This is the first clinical trial using non-viral vector EVs to treat rare diseases including DMD.

3) Broad-spectrum applicability : Applicable to patients with all mutation types, including nonsense mutations and frameshift mutations;

4) Repeatable dosing : Break through the single-treatment limitation of AAV therapy due to immunogenic response and implement a repeated dosing strategy that adjusts the delivered mRNA dose based on the patient's recovery condition.

Based on the good preclinical data, the team decided to formally launch the IIT study, hoping that the success of this trial will provide more data on the safety and effectiveness of gene therapy for DMD.

https://news.yaozh.com/archive/45774.html