Gene therapy has shown promise in treating various diseases, but for conditions like muscular dystrophies, where genes are extremely large, delivery methods are limited. A new technology, called StitchR, divides the gene into two halves, which generate messenger RNAs that combine to restore the expression of missing or inactive proteins. StitchR successfully restored levels of therapeutic muscle proteins in animal models of muscular dystrophy, addressing the need for efficient delivery of large therapeutic genes.
The technology was developed by a team led by Douglas M. Anderson, PhD, at the University of Rochester. StitchR was able to restore expression of the proteins Dysferlin and Dystrophin, which are lacking in limb girdle and Duchenne muscular dystrophy, respectively. Duchenne muscular dystrophy is a common form of the disease that affects boys, leading to mobility issues and premature death. Individuals with limb girdle muscular dystrophy experience weakness and wasting in muscles, impacting their daily lives.
StitchR relies on self-cleaving ribozymes to join two separate mRNAs seamlessly within the cell, enabling the production of full-length functional proteins. The team optimized the process to increase efficiency and adapted it for gene delivery using adeno-associated virus vectors, a safe choice for gene therapy. StitchR has the advantage of producing only full-length proteins, unlike other dual vector approaches that may generate incomplete products.
The technology has demonstrated versatility, potentially being used with different vectors and mRNA sequences for various diseases. StitchR has been tested with multiple genes and sequences, showing promise for a wide range of applications. Only full-length proteins are produced, distinguishing StitchR from other similar technologies that may yield incomplete products. The team is now collaborating with other research labs to develop StitchR vectors for treating numerous diseases caused by large genes.
The research was published in the journal Science and funded by the University of Rochester, Jain Foundation, CANbridge Pharmaceuticals, and Scriptr Global, Inc. Anderson, a co-founder of Scriptr Global, Inc., holds patent applications related to StitchR and other RNA-based technologies. The team is dedicated to advancing research towards treatments for debilitating genetic diseases, many of which currently have no cure. These efforts highlight the potential of gene therapy and innovative technologies like StitchR in addressing challenging diseases and improving outcomes for patients.