Speaker 

Dr Julien Baruteau is a MRC Clinician Scientist Fellow at University College London Great Ormond Street Institute of Child Health, and Consultant in Metabolic Medicine at Great Ormond Street Hospital for Children, London. His research focuses on studying the pathophysiology and developing novel therapies for inherited metabolic diseases. He is developing gene therapy using both viral and non-viral vectors and has expertise in translating academic and industry-led programmes of gene therapies into first-in-human clinical trials. 

Gene therapy for inherited metabolic disorders: best approaches for different disorders

Gene therapy for monogenic disorders had been developed for the last 4 decades, marked by phenomenal success and fatal adverse events. Inherited metabolic diseases (IMDs) are ideal target for gene therapy due to their high unmet needs and have always been at the forefront of gene therapy innovation. 

The preclinical development of gene therapy technologies for IMDs is progressing fast. We will discuss how to mediate gene therapy in a cell at the nuclear or cytoplasmic level, the benefit and challenges of gene therapy through integration or not, long-term efficacy or not, the role of the immune system. 

We will present different gene therapy approaches with integrating ex vivo and in vivo vectors (e.g. lentiviral gene therapy), non-integrating in vivo vectors (e.g. adeno-associated viral vectors (AAV)), RNA therapies (e.g. messenger RNA, long non coding RNA, RNA interference, antisense oligonucleotides). 

Translation of these complex technologies in rare diseases remains a severe bottleneck, which needs to be solved. We will review recently disclosed interim results of innovative gene therapy clinical trials and discuss how these gene therapies could be implemented in our therapeutic strategies in the future.