We are seeking novel gene therapeutic technologies to selectively normalize or reduce the expression of abnormal repeat expansions. This includes approaches that utilize Adeno-Associated Virus (AAV)-derived nucleic acids, proteins (peptides), and regulatory factors to inhibit transcription or promote the degradation of repeat sequences. Additionally, we are interested in AAV-derived genome editing technologies that have unique features regarding editing efficiency, versatility, and safety for normalizing repeat sequences.

Solutions of interest include:

• AAV-mediated allele-specific gene silencing to selectively target mutated alleles while preserving normal gene function.
• CRISPR-based editing or other high-fidelity genome editing tool to ensure precise repeat sequence targeting and minimize off-target effects.
• Models that mimic human repeat expansion mutations for in-depth testing and preclinical evaluation, including patient-derived induced pluripotent stem cell (iPSC) models, organoid models, and transgenic animal models.

Our must-have requirements are:

• The technology should be easy to incorporate into AAV for gene therapy applications.
• The approach should be designed to specifically target and modify abnormal repeat expansions, minimizing the risk of off-target effects.

Our nice-to-have's are:

• The technology should ideally be unique and applicable to multiple trinucleotides repeat disorders.
• Animal or in vivo data available.
• Data showing low risk of immunogenicity and genetic variation.
• In vitro data should demonstrate the effect of shortening (repairing) elongation repeats in cultured cells.

What's out of scope:

• Small molecules
• Simple antisense oligonucleotides (ASOs) targeting disease-specific target genes