Robin E. Offord

Dr. Robin E. Offord was a pioneer of protein semisynthesis who demonstrated how chemically synthesized peptides could be combined with naturally derived protein fragments to create modified proteins for fundamental research and therapeutic applications. His later work on chemokine engineering produced potent HIV entry inhibitors now advancing toward clinical use as topical microbicides for preventing sexual transmission of infection.

Offord was born on June 28, 1940, in Stondon, United Kingdom. He received his Ph.D. from Cambridge University, where he trained at the Medical Research Council Laboratory of Molecular Biology. During his years at Cambridge and Oxford from 1962 to 1980, he collaborated with four Nobel laureates: Frederick Sanger, César Milstein, Dorothy Hodgkin and Aaron Klug. He taught biochemistry at Oxford University for fourteen years before moving to Switzerland in 1980.

At the University of Geneva, Offord became Professor and Director of the Department of Medical Biochemistry in the Faculty of Medicine. He served as President of the School of Basic Medicine and hosted Martin Rodbell, later a 1994 Nobel laureate, as a visiting member of his laboratory in the early 1980s. He became Emeritus Professor in October 2005.

Offord's early research established the conceptual and practical foundations of protein semisynthesis. In 1970 he reported protected intermediates for preparing semisynthetic insulins, demonstrating that natural proteins could be selectively cleaved and religated with synthetic fragments bearing modifications at defined positions. His 1980 monograph Semisynthetic Proteins became the definitive reference for the field. The approach enabled site-specific introduction of isotopic labels, nonnatural amino acids and chemical probes into proteins that were otherwise inaccessible to total synthesis. His laboratory applied these methods to insulin, cytochrome c, lysozyme and other proteins, generating variants that revealed mechanisms of hormone action, electron transfer and enzyme catalysis.

In the late 1990s Offord turned his semisynthetic expertise toward HIV prevention. Working with Oliver Hartley, he engineered analogs of the chemokine RANTES that block CCR5, the principal coreceptor for HIV entry into target cells. Their first candidate, AOP-RANTES, incorporated nonnatural amino acids at the N-terminus to enhance antiviral potency. Through systematic medicinal chemistry optimization, they developed PSC-RANTES, a variant some fifty times more potent than the original that completely protected rhesus macaques from vaginal challenge with simian-human immunodeficiency virus. When applied topically at subnanomolar concentrations, PSC-RANTES induced prolonged internalization of CCR5, rendering cells resistant to infection for at least 24 hours.

To overcome the cost of chemical synthesis for developing-world applications, Offord and Hartley used phage display to discover fully recombinant analogs containing only natural amino acids. The lead compound 5P12-RANTES retains high potency without the inflammatory agonist activity of earlier variants. It has advanced through preclinical development and is being formulated as vaginal gels and sustained-release vaginal rings for prevention of sexual HIV transmission.

In 2005 Offord and Hartley founded the Mintaka Foundation for Medical Research in Geneva to develop affordable HIV prevention strategies for resource-limited settings. Under Offord's leadership as Executive Director, the foundation secured major funding from the Wellcome Trust and established collaborations with manufacturing partners to produce clinical-grade 5P12-RANTES at costs compatible with global health needs.

Offord was a co-founder of the Swiss Institute of Bioinformatics in 1998. He co-founded multiple biotechnology companies including Gryphon Sciences in 1994, Geneva Bioinformatics in 1998, and Geneva Proteomics in 2000, serving as the first president of GeneProt. He served as Chairman of the Advisory Board of Eclosion, Geneva's life-sciences incubator, and was a member of the Geneva government's Council for Regional Economic Development for ten years. He later served as Chairman of the Board of Trustees of the Torrey Pines Institute for Molecular Studies.

Offord joined the American Peptide Society in 1991. He served as Secretary of the Board from 2003 to 2011 and as a member of the Executive Committee from 2011 to 2017. He was elected President of the Board in 2013, becoming the first non-American to hold that office. In 2005 he received the Rao Makineni Lectureship recognizing his contributions to chemokine engineering for HIV prevention. He shared the 2002 Man of the Year award from the Swiss financial newspaper L'Agefi. At the 2017 American Peptide Symposium in Whistler, the Society recognized Offord for his outstanding and continuous service.

Offord died on March 11, 2021, in Geneva, Switzerland.