Advanced search
Publication Cover
Expert Opinion on Drug Delivery Volume 2, 2005 - Issue 1
Submit an article Journal homepage
248
Views
81
CrossRef citations to date
0
Altmetric
Review

Recent advances in the use of protein transduction domains for the delivery of peptides, proteins and nucleic acids invivo

Eric L Snyder UCSD School of Medicine, Howard Hughes Medical Institute and Department of Cellular & Molecular Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, USA. [email protected]
&
Steven F Dowdy UCSD School of Medicine, Howard Hughes Medical Institute and Department of Cellular & Molecular Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0686, USA. [email protected]
Pages 43-51 | Published online: 22 Apr 2005

  • JOLIOT A, PROCHIANTZ A: Transduction peptides: from technology to physiology. Nat. Cell Biol. (2004) 6:189–196.
  • TREHIN R, MERKLE HP: Chances and pitfalls of cell penetrating peptides for cellular drug delivery. Eur. j Pharm. and Biopharm. (2004) 58:209–223.
  • SCHWARZE SR, HO A. VOCERO-AKBANI A, DOWDY SF: In vivo protein transduction: delivery of a biologically active protein into the mouse. Science (1999) 285(5433):1569–1572. In vivo systemic delivery of enzymatically active TAT-fusion protein.
  • FRANKEL AD, PABO CO: Cellular uptake of the tat protein from human immunodeficiency virus. Cell (1988) 55(6):1189–1193.
  • GREEN M, LOEWENSTEIN PM: Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell (1988) 55(6):1179–1188.
  • ••These two papers ([41 and [51) providedthe first observations of protein transduction by the full-length TAT protein.
  • VIVES E, BRODIN P, LEBLEU B: A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J.Bio/. Chem. (1997) 272(25):16010–16017.
  • DEROSSI D, JOLIOT AH, CHASSAING G, PROCHIANTZ A: The third helix of the Antennapedia homeodomain translocates through biological membranes. J.Biol. Chem. (1994) 269(14): 10444–10450.
  • MM JC, SHEN H, WATKINS SC, CHENG T, ROBBINS PD: Efficiency of protein transduction is cell type-dependent and is enhanced by dextran sulfate. /Bid. Chem. (2002) 277:30208–30218.
  • WENDER PA, MITCHELL DJ, PATTABIRAMAN KP, PELKEY ET, STEINMAN L, ROTHBARD JB: The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proc. Nail. Acad. Sci. USA (2000) 97:13003–13008.
  • WADIA JS, DOWDY SF: Modulation ofcellular function by TAT mediated transduction of full length proteins. Curr. Prot. Pep. Sci. (2003) 4:97–104.
  • NAGAHARA H, VOCERO-AKBANI AM, SNYDER EL et al.: Transduction of full-length TAT fusion proteins into mammalian cells: TAT-p27Kipl induces cell migration. Nat. Med. (1998) 4(12):1449–1452.
  • •First description of the use of TAT-fusion proteins to modulate the intracellular biology of cultured mammalian cells.
  • LEWIN M, CARLESSO N, TUNG C-H, et al.: Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol (2000) 18:410–414.
  • EGUCHI A, AKUTA T, OKUYAMA H et al.: Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells. J.Bio/. Chem. (2001) 276:26204–26210.
  • TORCHILIN VP, RAMMOHAN R, WEISSIG V LEVCHENKO TS: TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc. Natl. Acad. Sci. USA (2001) 98:8786–8791.
  • TORCHILIN VP, LEVCHENKO TS, RAMMOHAN R, VOLODINA N, PAPAHADJOPOULOS-STERNBERG B, D'SOUZA GGM: Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome-DNA complexes. Proc. Natl Acad. Sci. USA (2003) 100:1972–1977.
  • •TAT-mediated delivery of GFP-encoding plasmid DNA to tumours in vivo.
  • WADIA JS, STAN RV, DOWDY SF: Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat. Med. (2004) 10:310–315.
  • ••This study demonstrates that cellularuptake of TAT-fusion proteins occurs by macropinocytosis, a specific form of endocytosis. Based on this knowledge of mechanism, the authors also describe a strategy for enhancing delivery of TAT-fusion proteins to the cellular interior.
  • DEROSSI D, CALVET S, TREMBLEAU A, BRUNISSEN A. CHASSAING G, PROCHIANTZ A: Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J. Biol. Chem. (1996) 271(30): 18188–18193.
  • RICHARD JP, MELIKOV K, VIVES E et al.: Cell-penetrating peptides: a re-evaluation of the mechanism of cellular uptake. J. Biol. Chem. (2002) 278:585–590.
  • LINDSAY MA: Peptide-mediated cell delivery: application in protein target validation. Curr. Opin. Pharmacol. (2002) 2:587–594.
  • VOUSDEN KH, LU X: Live or let die: the cell's response to p53. Nat. Rev. Cancer (2002) 2:594–604.
  • SNYDER EL, MEADE BR, SAENZ CC, DOWDY SF: Treatment of a terminal peritoneal carcinomatosis by a transducible p53-activating peptide. PLoS Biology (2004) 2:186–193.
  • ••Describes the use of a transducible p53-activating peptide to effectively treat three different models of cancer, resulting in long-term disease-free survival in one model. This peptide was stabilised by synthesis of a retro-inverso isoform, thus increasing its potency in vivo.
  • SELIVANOVA G, RYABCHENKO L, JANSSON E, IOTSOVA V, WIMAN KG: Reactivation of mutant p53 through interaction of a C-terminal peptide with the core domain. Md. Cell. Biol. (1998) 19:3395–3402.
  • SELIVANOVA G, IOTSOVA V, OKAN I et al: Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain. Nat. Med. (1997) 3:632–638.
  • KIM AL, RAFFO AJ, BRANDT-RAUF PW et al.: Conformational and molecular basis for induction of apoptosis by a p53 C-terminal peptide in human cancer cells. J. Biol. Chem. (1999) 274:34924–34931.
  • CHOREV M, GOODMAN M: A dozen years of retro-inverso peptidomimetics. Acc. Chem. Res. (1993) 26:266–273.
  • AARNT CR, CHIOREAN MV, HELDEBRANT MP, GORES GJ, KAUFMAN S: Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J. Biol. Chem. (2002) 277:44236–44243.
  • FULDA S, WICK W, WELLER M, DEBATIN K-M: Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat. Med. (2002) 8:808–815.
  • •Another report of long-term survival in a mouse model of cancer; in this case after co-administration of a transducible peptide and an extracellular anticancer agent.
  • VUCIC D, DESHAYES K, ACKERLY H et al.: SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP). J.Bio/. Chem. (2002) 277:12275–12279.
  • YANG L, MASHIMA T, SATO S et al: Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated smac peptide. Cancer Res. (2003) 63(4):831–837.
  • HARADA H, HIRAOKA M, KIZAKA-KONDOH S: Antitumor effect of TAT-oxygen-dependent degradation-caspase-3 fusion protein specifcally stabilized and activated in hypoxic tumor cells. Cancer Res. (2002) 62:2013–2018.
  • •The first demonstration that specific domains can be added to TAT-fusion proteins in order to control the cells in which they are active.
  • INOUE M, MUKAI M, HAMANAKA Y, TATSUTA M, HIRAOKA M, KIZAKA-KONDOH S: Targeting hypoxic cells with a protein prodrug is effective in experiment malignant ascites. Int. J. Onc. (2004) 25:713–720.
  • WILLAM C, MASSON N, TIAN Y et al:Peptide blockade of HIF-alpha degradation modulates cellular metabolism and angiogenesis. Proc. Natl Acad. Sci. USA (2002) 99(10:10423–10428.
  • MENDOZA N, FONG S, MARSTERS J, KOEPPEN H, SCHWALL R, WICKRAMASINGHE D: Selective cyclin-dependent kinase 2/cyclin a antagonists that differ from ATP site inhibitors block tumor growth. Cancer Res. (2003) 63(5): 1020–1024.
  • HARBOUR JW, WORLEY L, MAD, COHEN M: Transducible peptide therapy for uveal melanoma and retinoblastoma. Arch. Opthalmmol (2002) 120:1341–1346.
  • MAI JC, MI Z, KIM S-H, NG B, ROBBINS PD: A proapoptotic peptide for the treatment of solid tumors. Cancer Res. (2001) 61:7709–7712.
  • DATTA K, SUNDBERG C, KARUMANCHI SA, MUKHOPADHYAY D: The 104-123 amino acid sequence of the beta-domain of von Hippel-Lindau gene product is sufficient to inhibit renal tumor growth and invasion. Cancer Res. (2001) 61:1768–1775.
  • HOSOTANI R, MIYAMOTO Y, FUJIMOTO K et al.: Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice. Clin. Cancer Res. (2002) 8:1271–1276.
  • BORSELLO T, CLARKE PGH, HIRT L et al.: A peptide inhibitor of c-Jun N terminal kinase protects against excitoxicity and cerebral ischemia. Nat. Med. (2003) 9:1180–1186.
  • •One recent example of the many papers showing that transducible peptides and proteins are effective in the treatment of rodent stroke models. Also notable for the use of a stabilised retro-inverso peptide.
  • HIRT L, BADUAT J, THEVENET J et al: D-JNK1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia. Stroke (2004) 35:1738–1743.
  • AARTS M, LIU Y, LIU L et al.: Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions. Science (2002) 298:846–850.
  • CAO G, PEI W, GE H et al: In vivo delivery of a Bc1-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. j Neurosci. (2002) 22:5423–5431.
  • KILIC E, DIETZ GPH, HERMANN DM, BAHR M: Intravenous TAT-Bc1-xL is protective after middle cerbral artery occlusion in mice. Ann. NeuroL (2002) 52:617–622.
  • DIETZ GPH, KILIC E, BAHR M: Inhibition of neuronal apoptosis in vitro and in vivo using TAT-mediated protein transduction. Mol Cell. Neurosci. (2002) 21:29–37.
  • ASOH S, OHSAWA I, MORI T et al: Protection against ischemic brain injury by protein therapeutics. Proc. Natl Acad. Sci. USA (2002) 99:17107–17112.
  • BRIGHT R, RAVAL AP, DEMBER JM et al.: Protein Kinase C delta mediates cerebral reperfusion injury in vivo. J. Neurosci. (2004) 24(31):6880–6888.
  • CHEN L, HAHN H, WU G et al.: Opposing cardioprotective actions and parallel hypertrophic effects of deltaPKC and epsilonPKC. Proc. Natl Acad. Sci. USA (2001) 98(20):11114–11119.
  • INAGAKI K, CHEN L, IKENO F et al.: Inhibition of {ö}-protein kinase c protects against reperfusion injury of the ischemic heart in vivo. Circulation (2003) 108(19):2304–2307.
  • GUSTAFSSON AB, SAYEN MR, -WILLIAMS SD, CROW MT, GOTTLIEB RA: TAT protein transduction into isolated perfused hearts. Circulation (2002) 106:735–739.
  • MYOU S, ZHU X, MYO S et al.: Blockadeof airway inflammation and hyperresponsiveness by HIV-TAT-dominant negative Ras/ Immunol (2003) 171(8):4379–4384.
  • MYOU S, LEFF AR, MYO S et al.: Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. J. Exp. Med. (2003) 198(10):1573–1582.
  • CLOHISY JC, ROY BC, BIONDO C et al.: Direct inhibition of NF-{K}B blocks bone erosion associated with inflammatory arthritis. J. Immunol. (2003) 171(10):5547–5553.
  • MAY MJ, D-ACQUISITO F, MADGE LA, GLOCKNER J, POBER JS, GHOSH S: Selective inhibition of NF-KB activation by a peptide that blocks the interaction of NEMO with the IKB kinase complex. Science (2000) 289:1550–1554.
  • BUCCI M, GRATTON J-P, RUDIC RD et al: In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat. Med. (2000) 6:1362–1367.
  • KRAUTWALD S, ZIEGLER E, TIEDE K, PUST R, KUNZENDORF U: Transduction of TAT-FLIP fusion protein results in transient resistance to Fas-induced apoptosis in vivo. J. Biol. Chem. (2004):M401327200.
  • EUM WS, CHOUNG IS, LI MZ et al.: HIV-1 TAT-mediated protein transduction of Cu,Zn-superoxide dismutase into pancreatic beta cells in vitro and in vivo. Free Radic. Biol. Med. (2004) 37:339–349.
  • BLUM S, DASH PK: A cell-permeable Phospholipase Cyl-binding peptide transduces neurons and impairs long-term spatial memory. Learning Memory (2004) 11:239–243.
  • •Transducible peptides can be used to modulate and study higher cognitive functions such as memory retention.
  • SUGIOKA R, SHIMIZU S, FUNATSU T et al.: BH4-domain peptide from Bc1-xL exerts anti-apoptotic activity in vivo. Oncogene (2003) 22(52):8432–8440.
  • HASHIDA H, MIYAMOTO M, CHO Y et al.: Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool. Br. J. Cancer (2004) 90:1252–1258.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.