Enrico Mastrobattista: Restoring genetic defects using CRISPR/Cas9 in nanoparticles
Dr. Enrico Mastrobattista is an expert in research into packaging DNA and proteins into nanoparticles for targeted delivery to diseased cells in the body. With his Vici grant, he aims to utilise his expertise to develop a therapy for diseases caused by genetic defects. To that end, he will look for nanoparticles that can deliver the revolutionary CRISPR/Cas9 system to diseased cell in the patient’s body, in order to repair the genetic defect.
More than 4,000 currently known conditions are caused by genetic defects. For many of these conditions, no treatment is currently available, or the symptoms are treated by a life-long course of medication. The CRISPR/Cas9 system, which was developed at an American university six years ago, seemed to finally offer a potential for cures for these diseases. The system cuts the DNA in a cell in precisely the desired location and facilitates the endogenous repair of the damaged genes. “However, it is now clear that there are several shortcomings that limit the therapeutic application of CRISPR/Cas9 in humans”, Mastrobattista explains.
One of these shortcomings is that the body recognizes the CRISPR/Cas9 system as foreign and tries to break it down as quickly as possible. Secondly, to be effective, the CRISPR/Cas9 system should be delivered INSIDE diseased cells, which is troublesome due to the large size of these biomacromolecules. Finally, in addition to cutting the DNA in the desired location, it also often cuts DNA in locations where it was not intended to be cut.
SERIOUS LIVER DISEASE
Based on his experiences in precisely packaging and administering DNA and proteins, Mastrobattista has come up with a strategy for dealing with these problems with the CRISPR/Cas9 system. He hopes to use this strategy to develop an application that can be tested in a mouse model for serious liver diseases. He also plans on studying several other strategies for preventing unwanted immune reactions.
Enrico Mastrobattista studied Medical Biology at Utrecht University, where he also earned his PhD in Drug Delivery. From there, he went to Cambridge as a Marie Curie Fellow to work in the group led by Prof. Andrew Griffiths, studying the directed evolution of enzymes in synthetic cells at the prestigious MRC Laboratory of Molecular Biology. Upon his return to Utrecht, he was awarded a Vidi grant to elaborate the technology for applications in gene therapy. In 2013, he received the Galenus research award (Prix Galien) for his research into nanomedicines for biopharmaceuticals. Thanks to his expertise in the field, he has been involved in several European partnership efforts, and in addition to his many publications, he also has five patents to his name.
Read more about Enrico Mastrobatista’s research.