At 11am (GMT) on Monday 11th November, Adrian R. Krainer will present the 2024 Max Perutz Lecture titled, ‘Antisense Modulation of RNA Splicing for Rare Disease Therapy.’ The lecture will be delivered in the LMB’s Max Perutz Lecture Theatre, and anyone interested is warmly invited to attend; if you are not at the LMB and wish to attend a seminar, please contact the seminar secretary.
Adrian Krainer is the St. Giles Foundation Professor and Cancer Center Program Co-Leader at the Cold Spring Harbor Laboratory, New York. There, his group investigates the mechanisms of mRNA splicing, including how it is dysregulated in the context of genetic diseases and cancers, and how these defects may be corrected as possible therapeutic interventions.
This research has been notably successful in the study of spinal muscular atrophy (SMA), a neuromuscular disorder that results in muscle wasting and was the leading genetic cause of death in infants. In SMA, the SMN1 gene is defective, and the SMN2 gene is present but it is spliced incorrectly. Adrian’s group developed an effective therapeutic approach to correct this defect by stimulating SMN protein production by altering mRNA splicing via the introduction of a chemically modified strand of RNA known as an antisense oligonucleotide (ASO). Development of this ASO resulted in the first approved drug for SMA. Adrian’s group is currently seeking to advance antisense therapeutic approaches for various cancers.
Adrian’s research achievements have been recognised with several prestigious awards, including the Albany Medical Center Prize in Medicine and Biomedical Research (2024), the Wolf Prize in Medicine (2021), and the Life Sciences Breakthrough Prize (2019). Adrian was elected to the American Academy of Arts and Sciences, the National Academy of Inventors, the National Academy of Medicine, and the National Academy of Sciences.
Lecture abstract
I will describe the design, development, and therapeutic applications of antisense oligonucleotides (ASOs) that alter the splicing patterns of, and/or degrade, target transcripts. I will focus on CNS (Central Nervous System) indications, including the development and clinical impact of nusinersen (Spinraza)—the first approved drug for spinal muscular atrophy—as well as our ongoing preclinical development of ASOs for a lethal paediatric brain cancer, H3K27M-altered diffuse midline glioma.
Background information
The Max Perutz lecture is named in honour of LMB Nobel Laureate Max Perutz. It is one of a series of named lectures organised by the LMB and given by eminent scientists from around the world. These talks are supported financially by AstraZeneca and the Max Perutz Fund.
Max Perutz first arrived in Cambridge in 1936 as a research student to study X-ray crystallography at the Cavendish Laboratory under J. D. Bernal. He soon became a world leader in the field of molecular biology, developing a novel technique to determine the structure of proteins. Max is a central figure in the LMB’s history: he was the first Director of the ‘MRC Unit for Research on the Molecular Structure of Biological Systems’ upon its establishment in 1947 and became the first Chairman of the unit when it became the MRC Laboratory of Molecular Biology in 1962. In this year, he was also awarded the Nobel Prize in Chemistry jointly with John Kendrew for their studies on protein structures. He remained at the helm of the LMB as the lab grew to be a preeminent research institute, before retiring in 1979. He died on 6 February 2002, aged 87, in Cambridge.
Further references
Adrian R. Krainer – Cold Spring Harbor Laboratory
LMB Named Lectures
Max Perutz