Chinese Scientists Achieve Breakthrough in Gene Therapy

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Chinese medical researchers have achieved a significant breakthrough in gene therapy technology by developing a method that overcomes the previous limitations of vector carrying capacity. This advancement could significantly accelerate the clinical use of gene therapy for various health conditions, including autism and epilepsy.

A collaborative effort between scientists at the Shenzhen Institutes of Advanced Technology and a leading hospital in Beijing has led to the creation of a novel gene therapy approach called AAVLINK. This method markedly improves the ability of the adeno-associated virus (AAV) vectors to carry genetic material, as detailed in a recent publication in a prominent life sciences journal.

Gene therapy typically involves inserting therapeutic gene segments into specific cells using vectors to correct genetic anomalies or defects. AAV is considered an ideal vector due to its safety and efficiency, but its capacity is limited to approximately 4,700 base pairs, or 4.7 kilobases. Many disease-causing genes, including those linked to autism and epilepsy, are much larger than this, which has historically restricted progress in developing effective gene treatments for these conditions.

Additionally, current strategies that rely on dual AAV vectors face obstacles such as low efficiency in recombination and the production of ineffective or potentially harmful proteins, complicating efforts to achieve safe and effective therapies.

To overcome these challenges, the researchers split the large target gene into two parts, each packaged into separate AAV vectors. They utilized a sophisticated DNA recombination technique that allows the two parts to recombine precisely once inside the cell, resulting in the expression of the full functional gene.

Animal tests demonstrated that this AAVLINK method successfully reconstructed full-length versions of important genes associated with autism, like Shank3, and epilepsy, such as SCN1A. This reconstruction led to noticeable improvements in the behavior and symptoms of the test subjects.

Building on this success, the research team developed a comprehensive toolkit for delivering long genes via AAV vectors and systematically examined 193 human disease-related genes longer than 4,000 base pairs. These genes are implicated in a range of illnesses, including muscular dystrophy, hereditary deafness, and retinal disorders, with the largest gene exceeding 11,000 base pairs.

Moving forward, scientists aim to refine the delivery efficiency of the AAVLINK system, create disease-specific gene therapy models, and conduct extensive preclinical studies in primates. These efforts are intended to bring this innovative technology closer to clinical application and broader medical use.