Lentiviral vector for ALS

About

Overview While gene therapy for ALS shows promise, existing delivery technologies are limited. Lentiviral vectors are powerful gene delivery vehicles that integrate into the host genome of dividing and non-dividing cells allowing long-term transgene expression. Their versatility is increased by a ability to incorporate heterologous viral envelope proteins onto the vector particles instead of the native envelope, conferring on these pseudotyped vectors a modified tropism and host range specificity. Imperial College team has developed novel, targeted vectors to deliver genes directly to motor neurons from a minimally invasive, peripheral injection site.   Key features: Antibody conjugated lentiviral vectors for specific tropism to neuromuscular junction Surface engineering targets vectors specifically for motor neurons (MNs) Vectors can be retrograde transported to spinal cord and transduce spinal motor neurons upon peripheral muscle delivery. In vivo data confirms targeted delivery and neuroprotective effects in model of ALS. Robust long-term expression followed for three months post transduction and absence of neuroinflammation, coupled the selective tropism indicates that these vectors are applicable for gene therapy in the CNS. These vectors can be further utilised to induce and characterise models of epilepsy and autism spectrum disorder, modulate specific cell populations in neurodegenerative disease and brain injury and finally, identify the neural CHIKV entry receptor. Development stage Next steps include preclinical data package, further understanding which transgene to deliver for given indications, testing dose and dose frequency for long-lasting effect. Imperial Innovations is seeking codevelopment or licensing partners for this technology.   Intellectual property Composition of matter and method of use are protected by international patent application published as WO/2014/184562.