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Dr. Alan Thierry

al-thierry@orange.fr

Senior Investigator Gene Therapy

Researcher in

Research Project Area: 

Development of synthetic vector for Gene transfer in stem cells.

Positions Held: 

2008-present
Part-time Researcher
REMEDI
Development of synthetic vector for Gene transfer in stem cells

2001-2007
Associate Professor
Université Montpellier 2, France
Development of delivery systems for macromolecules;
Complex systems for the compaction of nucleic acids

1997-2000
Department Director
Biovector Ther., Labège, France
Development of synthetic vector for Gene transfer

1992-1996
Visiting Scientist
NCI, NIH, Bethesda, USA
Development of synthetic vector for Gene transfer
 

Awards & Honours: 

2004
Qualification from the Ministere de l’Education Nationale for the position of Professeur des Universités (Cellular Biology)

2002
National award for the innovative project, 400,000€

1994
Federal Technology Cash Award from the National, Cancer Institute, National Institutes of Health, Bethesda, USA.
 

Selected Publications: 

1.Vignon, J., Privat, A. , Chaudieu, I., Thierry, A., Kamenka, J.M., and Chicheportiche, R. : [3H] thienyl-phencyclidine binds to two different sites in rat brain.
Brain Res. 378 : 133-141, 1986

2.Madelmont, J.C., Godeneche, B., Labarre, P., Thierry, A., and Veyre, A. : Comparative study of the efficiency of 2-chloroethyl and 2-fluoroethyl nitrosoureas.
Eur. J. Med. Chem. 22 : 261-264, 1987

3.Thierry, A. and Chicheportiche, R. : Use of ATP bioluminescence measurements for the estimation of biomas during biological humification.
Appl. Microbiol Biotechnol. 28 : 199-202, 1988

4.Thierry, A. Doly, M., Braquet, P., Cluzel, J., and Meyniel, G.: Presence of specific platelet-activating factor binding sites in the rat retina.
Eur. J. Pharmacol. 163 : 97-101, 1989

5.Thierry, A., Jorgensen, T., Forst, D., Belli, J.A.., Dritschilo, A., and Rahman, A. : Modulation of multidrug resistance in Chinese hamster cells by liposome-encapsulated doxorubicin.
Cancer Commun. 1 : 311-316, 1989.

6.Godeneche, D., Rapp, M. Thierry, A., Laval, F., Madelmont, J.C., Chollet, P. and Veyre, A. : DNA damage induced by a new chloroethyl nitrosourea on malignant melanoma cells. Cancer Res. 50 : 5898-5903, 1990.

7.Thierry, A.R., Dritschilo, A., and Rahman, A. : Liposomal carrier system as a novel approach to transport ologonucleotides into cells.
Proc. Am. Assoc. Cancer Res. 31/2642, 1990

8.Oudard, S., Thierry, A., Jorgensen, T.J., and Rahman, A : Senzitization of multidrug-resistant colon cancer cell lines to doxorubicin encapsulated in liposome.
Cancer Chemother. Pharmacol. 28: 259-265, 1991
9.Thierry, A.R., and Dritschilo, A.: Intracellular avaibility of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity.
Nucleic Acids Res. 21: 5691-5698, 1992

10.Thierry, A.R., Dritschilo, A. and Rahman, A : Effect of liposomes on P-glycoprotein function in multidrug resistance cells.
Biochem. Biophys. Res. Commun. 187 : 1098-1105, 1992

11.Thierry, A.R., and Dritschilo, A. : Liposomal delivery of antisense oligodeoxynucleotides : Application to the modulation of multidrug resistance in cancer cells.
Ann. NY Acad. Sci. 660 : 300-302, 1992

12.Thierry, A.R. Rahman, A. , and Dritschilo, A. : Overcoming multidrug resistance in human tumor cells using free and liposomally encapsulated antisense oligodeoxynucleotides.
Biochem. Biophys. Res. Commun. 190 : 952-960, 1993

13.Thierry, A.R., Bradley, M.O., and Chrisey, L.A.: Progress in antisense research and development.
Antisense Res. Dev. 3 : 411-416, 1993

14.Thierry, A.R., Vige, D., Belli, J.A., Dritschilo, A. , and Rahman, A. : Modulation of doxorubicin resistance in multidrug resistance cancer cells by liposomes.
FASEB. J. 7572-579, 1993

15.Rahman, A., Thierry, A.R., Husain, S.R., and Dritschilo, A.: Clinical evaluation of liposome encapsulated doxorubicin and the modulation of multidrug resistance in cancer cells. J. Liposome Res. 4 : 167-192, 1994

16.Lisziewicz, J. Sun, D. Weichold, F.F., Thierry, A.R., Lusso, P. Tang, J. Gallo, R.C., and Agrawal, S. : Antisense oligodeoxynucleotide phosphorothioate complementary to Gag mRNA blocks replication of human immunodeficiency virus type 1 in human peripheral blood cells;
Proc. Natl. Acad. Sci. USA 91, 7942-7946, 1994

17.Thierry, A.R., Bryant, J.L., Aksentijevich, I. et al : Transgene expression in mice using a new liposomal delivery system.
AIDS Res. Hum. Retrov. 10, sup 3, 1994.

18.Lunardi-Iskandar, Y., Bryant, J.L., Zeman, R.A., Lam, V.H. Samaniego, F. Besnier, J.M., Hermans, P. Thierry, A.R., Gill, P., and Gallo, R.C.: Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immonodeficient mice blocked by an human pregnancy hormone.
Nature 375 : 64-68, 1995.

19.Thierry, A.R.,Rahman, A., and Dritschilo, A. : A new procedure for the preparation of liposomal doxorubicin : biological activity in multidrug-resistant tumor cells.
Cancer Chemother. Pharmacol. 35, 84-88, 1994.

20.Thierry, A.R., Zeman, R.A., Hunh, J.W., Bryant, J.L., Gallo, R.C. and Lunardi-Iskandar, Y. : In vitro and in vivo inhibition of tumorigenicity of neoplastic Kaposi's sarcoma cell line (KS Y – 1) by liposomal IL-6, IL-8 and VEGF antisense oligodeoxynucleotides.
Proc. Am. Assoc. Cancer. Res. 36, 413, 1995.

21.Thierry, A.R., Lunardi-Iskandar, Y, Bryant, J.L., Rabinovitch, P., Gallo, R.C., and Mahan, L.C. : Systemic gene therapy : biodistribution and long-term expression of a transgene in mice.
Proc. Natl. Acad. Sci. USA. 92, 9742-9746, 1995.

22.Aksentijevish, I. Pastan, Y. Lunardi-Iskandar, R. C. Gallo, M. M. Gottesman, and A. R. Thierry. In vitro and in vivo liposome-mediated gene transfer leads to human MDR1 expression in mouse bone marrow progenitor cells.
Human Gene Ther. 7:1111-1122, 1996.

23.M. Baudard, T.R. Flotte, J.M. Arian, A.R. Thierry, I.Pastan, M.G. Pang, W.G. Kearns, M.M Gottesman. Expression of the Human Multidrug Resistance and Glucocerebrosidase cDNAS from Adeno-Associated Vectors : Efficient Promoter Activity of AAV Sequences and in vivo Delivery via liposomes.
Human. Gene Ther. 7 :1309-1322, July 10, 1996.

24.A.R. Thierry, P. Rabinovich, B. Peng, L. C. Mahan, J. L. Bryant, and R. C. Gallo. Characterization of liposome-mediated gene delivery : Expression, stability and pharmacokinetics of plasmid DNA.
Gene Therapy 4:226-237, 1997.

25.C. Lavigne and A.R. Thierry. Enhanced antisense inhibition of human immunodeficiency virus type 1 in cell cultures by DLS delivery system.
Biochem.Biophys.Res.Comm. 237 (3):566-571, 1997.

26.G. B. Takle, A. R. Thierry, S. M. Flynn, B. Peng, L. White, W. Devonhish, R. A. Galbraith, A. R. Goldberg, and S. T. George. Delivery of oligoribonucleotides to human hepatoma cells using cationic lipid particles conjugated to ferric protoporphyrin IX (heme).
Antisense Nucl.Acid Drug Devlpt. 7:177-185, 1997.

27.A.R. Thierry. Optimization of lipoplex formulations for intravenous gene delivery.
J.Liposome Res. 7:143-159, 1997.

28.Felgner, P.L., Barenholz, Y., Behr, J.P., Cheng, S.H., Cullis, P., Huang, L., Jessee, J.A., Seymour, L., Szoka, F., Thierry, A.R., Wagner, E., and Wu, G. Nomenclature for synthetic gene delivery systems.
Hum. Gene Ther. 8, 511-512, 1997.

29.O. A. Sedelnikova, I. G. Panyutin, A. R. Thierry, and R. D. Neumann. Radiotoxicity of iodine-125-labeled oligodeoxyribonucleotides in mammalian cells.
J.Nucl.Med. 39 (8):1412-1417, 1998.

30.F. Samaniego, J.L. Bryant, N. Liu, J.E. Karp, A .R. Thierry, Y. Lunardi-Iskandar, R.C. Gallo. Induction of program cell death in Kaposi’s Sarcoma cells by preparations of human corionic gonadotropin.
J. NCI. 91, 135-142, 1999.

31.M. Schmutz, D. Durand, Y, Palvadeau, A. Debin, A. Etienne, A.R. Thierry. DNA packing in stable lipid complexes designed for gene transfer imitates DNA compaction in bacteriophages. Proc. Nat. Acad. Sci. USA 96, 12293-12298, 1999.

32.C. Lavigne, J. Yelle, G. Sauvé, A.R. Thierry. Lipid-based delivery of combinations of antisense oligodeoxynucleotides for the in vitro inhibition of HIV-1 replication.
AAPS Pharm. Sci. 3,article 7. 2001.

33.B. Tavitian, S. Marzabal, V. Boutet, B. Kuhnast, S. Terrazino, M. Moynier, F. Dollé, J.R. Deverre, A.R. Thierry. Characterization of a synthetic anionic vector for oligonucleotide Delivery using in vivo whole body dynamic imaging.
Pharm. Res. 19, 367-376, 2002.

34.C. Lavigne, J. Yelle, G. Sauvé, A.R. Thierry. On the sequence specific activity of antisense oligonucleotides aimed at the inhibition of HIV-1 replication.
AAPS Pharm. Sci., 4 article 9, (http ://www.pharmsci.org/) (2002).

35.A.R. Thierry, E. Vives, J.P. Richard, P. Prevot, C. Martinand-Mari, I. Robbins, B. Lebleu. Cellular Uptake and intracellular fate of antisense oligonucléotides.
Current Op. Mol. Ther. 5,133-138, (2003).

36.C. Lavigne, Y. Lunardi-Iskandar, B Lebleu, and A. R. Thierry. Cationic Liposomes/Lipids for Oligonucleotide Delivery: Application to the Inhibition of Tumorigenicity of Kaposi’s Sarcoma by VEGF Antisense Oligodeoxynucleotides.
Method Enzymol. 387, 189-210 (2004)

37.F.Maurel, F. Debart, F. Cavelier, A.R. Thierry, Lebleu Bernard, J.J Vasseur and E. Vivès. High yield synthesis of peptide-oligonucleotide chimera through a disulfide bridge: a simplified method for oligonucleotide activation.
Bioconjugate Chem., in press; available online via ScienceDirect DOI information: 10.1016/j.bmcl.2005.07.086 (2005)

38.Abes, S., Williams, D., Prevot, A. Thierry, P., Gait, M. J., and Lebleu, B. Endosome trapping limits the efficiency of splicing correction by PNA-oligolysine conjugates,
J Control Release 110(3):595-604 (2006)

39.A.R. Thierry, S. Abes, S. Resina, A. Travo, J.P. Richard, P. Prevot and B. Lebleu. Comparison of basic peptides- and lipid-based strategies for the delivery of splice correcting oligonucleotides.
Biochim.Biophys.Acta, 1758(3):364-74 (2006)

40.A.R. Thierry, F. Kepes, P. Amar, G. Barlovatz, G. Bernot, C. Froidevaux, J.L. Giavitto, J. Guespin, V. Norris, V. Schafter, C. Godin and F. Molina. Modelling of biological complex systems in the context of genomics,
J. Biol.Phys.Chem. 6, 103-107 (2006).

41.S. Resina, S. Abes, A. Travo, P. Clair, P. Prevot, R. Kole, B. Lebleu and A. R. Thierry. Switching on transgene expression by correcting aberrant splicing with using multi-targeting steric block oligonucleotides.
J. Gene Med. 9, 498-510 (2007).

42.M. Meryet-Figuières, S. Resina, C. Lavigne, G. Barlovatz-Meimon, B. Lebleu and A.R. Thierry. Inhibition of PAI-1 Expression in Breast Cancer Carcinoma Cells by siRNA at nanomolar range.
Biochimie 89, 1228-1233 (2007)

43.Resina S., Abes S., Turner J.J., Prevot P., Travo A., Clair P., Gait M.J., Thierry A.R., Lebleu B. Lipoplex and peptide-based strategies for the delivery of steric-block oligonucleotides.
Int J Pharm. 2007 May 17; [Epub ahead of print]

44.C. Lavigne and A.R. Thierry. Specific subcellular localization of siRNAs delivered by lipoplex in MCF-7 breast cancer cells.
Biochimie, 89, 1245-1251 (2007)

45.A.R. Thierry, Durand D., Schmutz M., and B. Lebleu DNA supramolecular self assemblies as a biomimetic complex system,
Emergent Properties in Natural and Artificial Dynamical Systems, in press.

46.A. De Guignée, A.R. Thierry, R. Ouellette, C. Lavigne. A rapid quantitative microwell cell-based fluorescence immunoassay for protein detection.
Biol. Res. ,accepted

47.M. Maltais, A.R. Thierry, T. Blessing, E. Maicas, M. Vert and C. Lavigne. A biodegradable hydrogel as a cell delivery carrier for autologous tumor cell vaccines,
Int.J.Oncol., acceptted.

48.S. Resina, P. Prevot, B. Lebleu and A.R. Thierry. The physico-chemical properties of the lipoplexes effect the mechanism of uptake and their oligonucleotides transfection activity.
Mol.Ther. submitted

49.V. Norris, A. Zemirline , P. Amar, E. Ben Jacob, G. Bernot, V. Danos, J.L. Giavitto, G. Hutzler, F. Kepes, O. Michel, G. Misevic, F. Molina, P. Stano and A.R. Thierry. Bactoputing Perspective: Computing with bacteria.
Submitted to Microbiology

50.D. Durand, Y, Palvadeau, M. Schmutz, B. Lebleu, A.R. Thierry. Biophysical properties of lipoplex formation. Abstract submitted to Nature Structural and Mol. Biol.

51.A.R. Thierry, O. Balland, A. Rastogi, C. Lavigne, M. Schmutz, D. Durand, Y, Palvadeau, B. Lebleu. Characterization of a new anionic synthetic vector for nucleic acids, in preparation

52.C. Lavigne, S. Arya, and A.R. Thierry. Challenge of HIV-1 infection with HIV-2 plasmid DNA delivered with lipoplex in CEM cells, in preparation.

Book Chapters:

53.Rahman, A., Dusre, L., Forst, D., Thierry, A., Roh, J.K and Treat, J. : Liposomal doxorubicin : preclinical and clinical data.
In: Horizons in Membrane Technology-progress in Clinical and Biological Research. New York, Alan R. Liss (Ed.), 1990 pp 281-302

54.Thierry, A., Rahman, A., and Dritschilo, A. : Liposomal delivery as a new approach to transport oligonucleotides.
In: Gene Regulation by Antisense RNA and DNA. Erickson, R.P. and Izant, J. (Eds), New York, Raven Press, 1992, pp 147-161

55.Thierry, A.R., and Tackle, G. : Liposomes as a delivery system for antisense and ribozyme compounds.
In: Delivery Strategies for Antisense oligonucléotides. Akhtar, S. (Ed.)Boca Raton, CRC press, 1995.

56.Thierry, A.R., Circumventing transport-associated resistance through drug delivery.
In: Drug Transport in Antimicrobial and Anticancer Chemotherapy. Georgopapadakou, N. (Ed.), New York, Marcel Dekker, Inc., p : 613-628, 1995.

57.A.R Thierry and L.C Mahan, Therapeutic Applications of lipid-based Gene Delivery systems,
In: Advanced Gene Delivery, A. Rolland (Ed.), 123, 1998.

58.A .R. Thierry. Transfert de gènes à l’aide de vecteurs synthétiques. In : Actualités de Chimie Thérapeutique,
In : Editions Scientifiques Médicales Elsevier, Paris, pp 101-103, 2001.

59.A. R. Thierry. Towards modelling and simulation of natural DNA compaction with a synthetic system. In: Modelling and simulation of biological processes in the context of genomics. Evry, pp167 (2004)

60.C. Godin, F. Molina and A.R. Thierry. Report of Conference synthesis In: Modelling of biological complex systems in the context of genomics. Genopole, P. Amar, F. Kepes, F. Molina and V. Norris, (Ed.), 2006.

 

Patents :

61.Thierry, A. et Chicheportiche, R. : Nouveau procedé d’humification. Brevet international deposé en 1986.

62.Rahman, A., Thierry, A.R. and Dritchilo, A. : Liposomal oligodeoxynucleotides and a method of using the same in therapeutics. , U.S Patent Application Serial N°08/483,090 GEORGETOWN UNIV.WASHINGTON DC, 1995.

63.Rahman, A., Thierry, A.R. and Dritchilo, A. : Method of encapsulating anthracycline in liposomes.; GEORGETOWN UNIV.WASHINGTON DC. Anonymous. USA:165000 (US5665710), 1993. 10-12-1993. admis le 3 Avril 1996.

64.Thierry, A .R. and Dritschilo, A. : Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacture and use therof for transfection of target cells. U.S Patent Application Serial N°08/483,090 GEORGETOWN UNIV.WASHINGTON DC, 1995.

65.Thierry, A.R. A liposomal delivery system for biologically active agents. Deposé le 7 Juin, 1995. The Government of the United States. Anonymous. USA:PCT/US95/09867(WO96/03977):1-55+25, 1996. 08-05-1995.

66.Thierry, A.R. Stable Particulate complexes with neutral or negative global charge of lamellar structure. BIOVECTOR:PCT/EP98/05103(WO99/06026):1-41 + 5, 1999. 07-30-1998
 

Professional and Personal Interests: 

Teaching: Biochemistry
Cellular Biology
Biotechnology and Intellectual property

Research: Drug Delivery: liposome, complex, controlled release system, biodistribution
Gene Therapy: synthetic vectors, plasmid DNA, oligonucleotide and SiRNA
Synthetic Biology: DNA auto-organization, complex systems
Drug Development: anticancer and antiviral agents, molecular therapy

Personal: Rugby, now as veteran’s player

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