biostudies-literatureMenacho-Melgar RNorth Carolina Biotechnology CenterNIGMS NIH HHS1-12https://www.ebi.ac.uk/biostudies/studies/S-EPMC7520907biostudies-literatureUnknown295The use of biologics (peptide and protein based drugs) has increased significantly over the past few decades. However, their development has been limited by their short half-life, immunogenicity and low membrane permeability, restricting most therapies to extracellular targets and administration by injection. Lipidation is a clinically-proven post-translational modification that has shown great promise to address these issues: improving half-life, reducing immunogenicity and enabling intracellular uptake and delivery across epithelia. Despite its great potential, lipidation remains an underutilized strategy in the clinical translation of lead biologics. We review how lipidation can overcome common challenges in biologics development as well as highlight gaps in our understanding of the effJournal of controlled release : official journal of the Controlled Release SocietyA review of lipidation in the development of advanced protein and peptide therapeutics.PMC7520907T32GM008555120439562018-BIG-6503T32 GM008555EE0007563Lynch MDHennigan JNDecker JSMenacho-Melgar RfalseA review of lipidation in the development of advanced protein and peptide therapeutics.The use of biologics (peptide and protein based drugs) has increased significantly over the past few decades. However, their development has been limited by their short half-life, immunogenicity and low membrane permeability, restricting most therapies to extracellular targets and administration by injection. Lipidation is a clinically-proven post-translational modification that has shown great promise to address these issues: improving half-life, reducing immunogenicity and enabling intracellular uptake and delivery across epithelia. Despite its great potential, lipidation remains an underutilized strategy in the clinical translation of lead biologics. We review how lipidation can overcome common challenges in biologics development as well as highlight gaps in our understanding of the eff2019-01-01T00:00:00Z2019 Feb2025-04-19T00:53:25.677Z2020-10-09T07:13:32ZS-EPMC75209073057998110.1016/j.jconrel.2018.12.032