Gene therapies, such as the use of adeno-associated viruses (AAV) are revolutionizing treatment for many important inherited disorders, offering the potential for curative intervention. A major challenge for AAV and other viral gene therapies is the immune response to the viral vector, limiting patient access and often precluding multiple dosing. At Evox, we are developing therapeutics based around exosomes loaded with AAV particles encoding the therapeutic gene of interest (ExoAAV), in effect cloaking them within the exosome and protecting them from the immune system. In addition, our ability to engineer exosomes to target particular tissue and cell types gives us more precise control in the choice of recipient cells for gene therapy.
Programmable gene editing tools such as CRISPR have the potential to revolutionise treatments for a wide range of diseases, such as genetic disorders and cancer. One of the key challenges in developing gene editing therapeutics is the ability to precisely deliver the gene editing molecular machinery to the target tissue and cell of interest, at a therapeutically relevant and safe level. At Evox, we are developing exosome systems that are capable of being targeted to different cells and tissues and that can efficaciously deliver CRISPR and other gene editing technologies to the precise cells of interest.
Nucleic acid-based therapeutics constitute a core therapeutic modality for Evox’s development programs, and we have sophisticated capabilities for the loading of various nucleic acids (primarily RNAs) into exosomes.
RNA loading is done via either proprietary exogenous or endogenous loading methods, enabling Evox to work across both natural and non-natural oligonucleotides. Solving the non-hepatic delivery challenge of nucleic acid-based drugs – such as siRNAs, anti-sense, mRNA or even gene editing modalities – is a core mission for Evox and tissue-targeted exosomes represent a very promising technology to achieve the delivery of RNA therapeutics.
Precision Therapeutic Targeting
Targeted delivery of nanoparticles is an area that has been intensively researched. Targeted drug delivery has a role to play in the delivery of many if not all drugs, but targeted delivery systems are critical for the delivery of nucleic acid-based agents such as siRNA and CRISPR-Cas technology.
Unlike many other nanoparticle-based delivery systems, exosomes are easily modified to contain targeting entities to enable tissue- and organ-specific delivery. Evox has created proprietary technology and knowhow to engineer and modify exosomes to facilitate targeted drug delivery to organs of interest, not least to the brain and the central nervous system. Our R&D teams are in constant pursuit of novel targeting technologies for enhancing exosome-mediated delivery to tissues of interest and combining this with the inherent biology of exosomes to further drive optimal in vivo behaviour.
Evox’s proprietary protein engineering technology enables loading of protein therapeutics and tissue targeting moieties onto the surfaces of exosomes, which allows targeting and display of therapeutic proteins to an organ of interest.
Additionally, Evox protein engineering strategies comprise methods for loading the inside of exosomes with various types of drug cargo, notably therapeutic proteins, and nucleic acids. This modification of the protein composition of exosomes is key to developing potent therapeutics harnessing both the native effects of exosomes and the specificity and affinity of conventional biologics.