BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:IMX Seminar Series - Stimuli-Responsive Coacervates as Universal C
 arriers for Intracellular Delivery of Macromolecular Therapeutics
DTSTART:20220411T131500
DTEND:20220411T141500
DTSTAMP:20260511T081237Z
UID:4159b225ac02eccf1d134a41709e2d27a3fda0532e8805b1875bb029
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Ali Miserez\, Nanyang Technological University\, Singapo
 re\nMacromolecular therapeutics (peptides\, proteins\, mRNAs\, plasmid DNA
 s\, etc…) hold vast therapeutic potential across human disease states by
  providing opportunities to address targets that have proven refractory to
  traditional approaches. However\, a critical impediment for the successf
 ul application of these modalities is their inability to cross cellular me
 mbranes\, preventing access to intracellular targets. Current approaches 
 to solve this key issue are based on nanoscale carriers to deliver the pay
 loads\, which however have several drawbacks including a tendency to get e
 ntrapped in endosomal compartments\, poor biodistribution\, and in some ca
 ses dose-limiting toxicity. Bypassing endosomal entrapment for direct cyto
 solic payload delivery is an attractive alternative approach but current m
 ethods suffer from their own pitfalls. For example\, the carriers are typi
 cally limited to delivery of a particular therapeutic modality or to relat
 ively low molecular weight (MW) cargos. Furthermore\, many approaches invo
 lve laborious synthetic procedures and/or encapsulation processes using or
 ganic solvents that can decrease bioactivity of the therapeutic cargo.\nIn
  this talk\, I will present a unifying delivery strategy of macromolecula
 r therapeutics recently developed by our team that is cargo-agnostic\, doe
 s not cross the cell membrane through classic endocytosis\, and non-cytoto
 xic. This new method exploits Liquid-Liquid Phase Separation (LLPS) of eng
 ineered peptides self-assembling into therapeutic-carrying coacervate mic
 rodroplets that are capable to release their cargo in the cytosol. These p
 eptide microdroplet carriers benefit from several unique advantages that s
 et them apart from other approaches:\n\n(1) A remarkable wide range of th
 erapeutics can be quickly recruited in the droplets\, from short therapeut
 ic anti-cancer stapled peptides to very large enzymes (430 kDa) to mRNAs\;
 \n(2) The recruitment process is rapid and carried out under aqueous envi
 ronments\, thus preserving bioactivity of the therapeutics. Furthermore\, 
 the recruitment efficiency is above 90% in all tested macromolecular thera
 peutics tested so far\;\n(3) The coacervates readily cross the cellular m
 embrane\, bypassing classical endocytosis pathways to enter in the cytosol
 \;\n(4) The side-chains of the peptides are conjugated with a redox-respo
 nsive moiety\, which triggers disassembly of the droplets in the reducing 
 environment of the cell\, leading to efficient payload release\;\n(5) Fin
 ally\, we have demonstrated that the bioactivity of the released therapeut
 ics is retained in the cell and that mRNAs exhibit high transfection effic
 iency.\n\nTogether\, this platform thus represents a general and robust st
 rategy for the intracellular delivery of a range of macromolecular modalit
 ies with promising potential for the treatment of a spectrum of human dise
 ases such as cancers\, metabolic diseases\, or genetic disorders. Further
 more\, these peptide coacervates could also be used as novel carriers for 
 next-generation mRNA-based therapeutics.\nReferences\n\n1.    Sun\, Y.
 \, Lim\, Z. W.\, Guo\, Q.\, Yu\, J. & Miserez\, A. Liquid–Liquid Phase S
 eparation of Proteins and Peptides Derived from Biological Materials: Disc
 overy\, Protein Engineering\, and Emerging Applications. MRS Bull 45\, 1
 039–1047 (2020). \n\n2.    Sun\, Y.\, Lau SY. Lim\, ZW.\, Chang\, S
 C.\, Ghadessy\, F.\, Partridge\, A. & Miserez\, A. Phase-Separating Peptid
 es for Direct Cytosolic Delivery and Redox-Activated Release of Macromolec
 ular Therapeutics. Nature Chemistry\, in press\, (2022).\n       
 https://www.nature.com/articles/s41557-021-00854-4\nBio: Ali Miserez is 
 a Full Professor of Biomimetic and Bioinspired Materials at Nanyang Techno
 logical University (Singapore)\, which he joined in 2009\, with joint appo
 intments in the School of Materials Science and Engineering and the School
  of Biological Sciences. He obtained his PhD (2003) from EPFL (Switzerland
 ) in the field of composite and mechanics of materials. From 2004 to 2009\
 , he was a post-doctoral fellow at UC Santa Barbara\, working in the lab o
 f Herbert Waite where he expanded his research towards biomimetic engineer
 ing and biochemistry of extra-cellular tissues. Miserez’s research aims
  at revealing the molecular\, physico-chemical\, and structural principles
  from unique biological materials\, and at translating their molecular des
 ign into novel biomimetic materials\, including for healthcare application
 s. At NTU\, he is currently the founding Director of the “Center for Sus
 tainable Materials”.\n\nHis interdisciplinary research has been publishe
 d in over 100 articles in a wide range of journals across the Physical and
  Life Sciences\, including in Science\, Nature Materials\, Nature Biote
 chnology\, Nature Chemical Biology\, Nature Chemistry\,Biomacromolecules
 \, ACS Nano\, Acta Biomaterialia\, Advanced Materials\, J. Biological 
 Chemistry\, Polymer Chemistry\, etc. He has delivered numerous invited t
 alks\, including at Gordon Research Conferences in the field of bioinspire
 d materials and biomineralization.\n 
LOCATION:https://epfl.zoom.us/j/68532296336?pwd=UXBrN1RBWHVFQjVjSko2NDF3S3
 Awdz09
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR