We are looking for innovative research projects that can identify and explore novel targets for gene therapy, particularly in CNS (central nervous system) and CVM (cardiovascular and metabolism) related diseases. We are interested in proposals that explore therapeutic effects through gene supplementation, knockdown, or a combination of both. The targets should be delivered by Adeno-Associated Virus (AAV) to the relevant tissues and cell types and should be distinguishable from existing therapies.

Solutions of interest include:

• Investigation of novel disease mechanisms and identification of gene targets that are not adequately addressed by existing therapies, focusing on approaches to target protein overexpression or harmful mutations using AAV-delivered RNA interference (RNAi) or CRISPR-based gene knockdown.
• In vitro models using human tissues or patient-derived cells for omics and genomic analysis that can evaluate pharmacological effects and validate selectivity of the knockdown.
• Exploratory research focusing on novel gene therapy targets with high clinical translatability, leveraging omics or genomic analysis from patient-derived tissues and cells to correlate target gene modulation with disease phenotypes.
• Use of novel CRISPR variants or alternative gene-editing technologies that limit off-target activity while delivering therapeutic effects via AAV.
• Research that can evaluate the pharmacological effects mediated by novel targets in in vitro/in vivo systems.
• AAV-delivered gene therapies that produce proteins, enzymes, or other therapeutic agents secreted into systemic circulation, addressing diseases that require widespread effects (e.g., lysosomal storage disorders), along with in vitro and in vivo models to monitor secretion levels and assess efficacy and safety.

Our must-have requirements are:

• The target must exhibit therapeutic effects in tissues and cell types that are accessible through AAV delivery, such as liver, muscle, or the central nervous system. This includes cases where the therapeutic effect is achieved by the drug being secreted into systemic circulation.
• For a novel target of single gene knockdown, the target should be limited to those that can be differentiated by gene therapy from existing therapies against the same target.

Our nice-to-have's are:

• An exploratory study of novel targets with clinical translatability using patient cells and tissues that allow for omics data analysis or genomic analysis.
• Genome editing technologies that offer higher selectivity for target sequences, ensuring high efficacy and safety.

What's out of scope:

• Diseases with a prevalence of less than 1 in 100,000 individuals in Japan and the US.
• Therapies aimed at treating cancer.