A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery

Katrin Hoffmann, Nadia Milech, Suzy M. Juraja, Paula T. Cunningham, Shane R. Stone, Richard W. Francis, Mark Anastasas, Clinton M. Hall, Tatjana Heinrich, Heique M. Bogdawa, Scott Winslow, Marie N. Scobie, Robert E. Dewhurst, Laura Florez, Ferrer Ong, Maria Kerfoot, Danie Champain, Abbie M. Adams, Susan Fletcher, Helena M. Viola & 10 others Livia C. Hool, Theresa Connor, Brooke A.C. Longville, Yew Foon Tan, Karen Kroeger, Volker Morath, Gregory A. Weiss, Arne Skerra, Richard M. Hopkins, Paul M. Watt

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.

Original languageEnglish
Article number12538
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

Cell-Penetrating Peptides
Cytoplasm
Peptide Nucleic Acids
Cell Engineering
Bacterial Genomes
Peptides
Muscular Dystrophies
Viral Genome
Endosomes
Life Expectancy
Oligonucleotides
Half-Life
Therapeutics

Cite this

Hoffmann, Katrin ; Milech, Nadia ; Juraja, Suzy M. ; Cunningham, Paula T. ; Stone, Shane R. ; Francis, Richard W. ; Anastasas, Mark ; Hall, Clinton M. ; Heinrich, Tatjana ; Bogdawa, Heique M. ; Winslow, Scott ; Scobie, Marie N. ; Dewhurst, Robert E. ; Florez, Laura ; Ong, Ferrer ; Kerfoot, Maria ; Champain, Danie ; Adams, Abbie M. ; Fletcher, Susan ; Viola, Helena M. ; Hool, Livia C. ; Connor, Theresa ; Longville, Brooke A.C. ; Tan, Yew Foon ; Kroeger, Karen ; Morath, Volker ; Weiss, Gregory A. ; Skerra, Arne ; Hopkins, Richard M. ; Watt, Paul M. / A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{34e592f7a26341368142da22e8e54db7,
title = "A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery",
abstract = "Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.",
author = "Katrin Hoffmann and Nadia Milech and Juraja, {Suzy M.} and Cunningham, {Paula T.} and Stone, {Shane R.} and Francis, {Richard W.} and Mark Anastasas and Hall, {Clinton M.} and Tatjana Heinrich and Bogdawa, {Heique M.} and Scott Winslow and Scobie, {Marie N.} and Dewhurst, {Robert E.} and Laura Florez and Ferrer Ong and Maria Kerfoot and Danie Champain and Adams, {Abbie M.} and Susan Fletcher and Viola, {Helena M.} and Hool, {Livia C.} and Theresa Connor and Longville, {Brooke A.C.} and Tan, {Yew Foon} and Karen Kroeger and Volker Morath and Weiss, {Gregory A.} and Arne Skerra and Hopkins, {Richard M.} and Watt, {Paul M.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-30790-2",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "1",

}

Hoffmann, K, Milech, N, Juraja, SM, Cunningham, PT, Stone, SR, Francis, RW, Anastasas, M, Hall, CM, Heinrich, T, Bogdawa, HM, Winslow, S, Scobie, MN, Dewhurst, RE, Florez, L, Ong, F, Kerfoot, M, Champain, D, Adams, AM, Fletcher, S, Viola, HM, Hool, LC, Connor, T, Longville, BAC, Tan, YF, Kroeger, K, Morath, V, Weiss, GA, Skerra, A, Hopkins, RM & Watt, PM 2018, 'A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery' Scientific Reports, vol. 8, no. 1, 12538. https://doi.org/10.1038/s41598-018-30790-2

A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery. / Hoffmann, Katrin; Milech, Nadia; Juraja, Suzy M.; Cunningham, Paula T.; Stone, Shane R.; Francis, Richard W.; Anastasas, Mark; Hall, Clinton M.; Heinrich, Tatjana; Bogdawa, Heique M.; Winslow, Scott; Scobie, Marie N.; Dewhurst, Robert E.; Florez, Laura; Ong, Ferrer; Kerfoot, Maria; Champain, Danie; Adams, Abbie M.; Fletcher, Susan; Viola, Helena M.; Hool, Livia C.; Connor, Theresa; Longville, Brooke A.C.; Tan, Yew Foon; Kroeger, Karen; Morath, Volker; Weiss, Gregory A.; Skerra, Arne; Hopkins, Richard M.; Watt, Paul M.

In: Scientific Reports, Vol. 8, No. 1, 12538, 01.12.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery

AU - Hoffmann, Katrin

AU - Milech, Nadia

AU - Juraja, Suzy M.

AU - Cunningham, Paula T.

AU - Stone, Shane R.

AU - Francis, Richard W.

AU - Anastasas, Mark

AU - Hall, Clinton M.

AU - Heinrich, Tatjana

AU - Bogdawa, Heique M.

AU - Winslow, Scott

AU - Scobie, Marie N.

AU - Dewhurst, Robert E.

AU - Florez, Laura

AU - Ong, Ferrer

AU - Kerfoot, Maria

AU - Champain, Danie

AU - Adams, Abbie M.

AU - Fletcher, Susan

AU - Viola, Helena M.

AU - Hool, Livia C.

AU - Connor, Theresa

AU - Longville, Brooke A.C.

AU - Tan, Yew Foon

AU - Kroeger, Karen

AU - Morath, Volker

AU - Weiss, Gregory A.

AU - Skerra, Arne

AU - Hopkins, Richard M.

AU - Watt, Paul M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.

AB - Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.

UR - http://www.scopus.com/inward/record.url?scp=85052147794&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-30790-2

DO - 10.1038/s41598-018-30790-2

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12538

ER -