CRISPR-Cas has been discovered in bacteria where it acts as an «immune system», protecting microorganisms from infectious agents. Since then it has been repurposed to become the most powerful tool to edit the DNA inside cells. This has sparked a revolution in the gene therapy field, allowing for the first time to design treatments for incurable genetic diseases.
Cas9 is the most advanced molecular scissor for the genome
Alia Therapeutics is leveraging on its proprietary CRISPR technology to develop first-in-class or best-in-class CRISPR-based medicines for rare genetic diseases.
Our synergic core technologies aim to solve two of the main issues connected with the application of CRISPR in the clinic.
Safety. Although Cas9 can be programmed to target a specific sequence of DNA, it may also cleave other genomic sequences which are very similar to the intended target and may be different by just few nucleotides. The cleavage of such sequences is known as off-target editing and must be absolutely avoided while using CRISPR to treat patients, as it may produce unwanted side effects.
At Alia Therapeutics we are exploiting a proprietary collection of Cas9 mutants with unprecedented specificity, among which evoCas9, one of the most specific Cas9 variants available to-date, although the search for new nuclease variants with desirable characteristics for therapeutic applications is still ongoing. The research leading to the discovery of evoCas9 has been published on Nature Biotechnology.
Delivery. One of the major obstacles in gene therapy is getting the editing tools into target cells safely and efficiently. Alia Therapeutics has developed new solutions to overcome this limitation.
- VEsiCas, vesicles for the traceless delivery of genome editing tools. These vesicles do not contain genetic elements and can efficiently deliver their protein payload (read: the CRISPR nuclease) into target cells. An innovative production platform allows to obtain a highly active genome editing product which combines the safety of protein delivery and the efficacy or viral vectors. You can read more about VEsiCas on Molecular Therapy – Nucleic Acids.
- lentiSLiCES, an all-in-one lentiviral vector to deploy a self-limiting genome editing circuit into target cells. The efficacy of lentiviral vector delivery is combined with the transient nature of the nuclease expression into target cells to minimize adverse effects. You can read more about lentiSLiCES on Nature Communications.