Name:

Dr. Marina Gottikh

Centre:

Belozersky Institute of Physico-Chemical Biology

The Moscow State University

Leniskie gory, MSU

Moscow  - Russia

Tel: +7 095 9395407    Fax: +7 095 9393181

e-mail: gottikh@belozersky.msu.ru

Head of the research team “Synthesis of modified oligonucleotides, cationic polymers and study of complex formation between them”. Her expertise is on modification of nucleic acids, especially antisense oligonucleotides, triple helix forming oligonucleotides and enzyme inhibitors, their interactions with proteins and their application as potential pharmacological agents. Oligonucleotide delivery inside cells by using polycationic vectors is one of the main goals of the research team.

Our work concerns with the syntheses and functionalisation of antisense oligonucleotides as well as the synthesis of cationic polymers, which may improve oligonucleotides penetration inside cells. Polymers that are under investigation, named Pluronics, are composed from three blocks: polypropylene oxide or polypropylene oxide (B)– polyethylene oxide (A). We expect that combination of cationic and membrane active blocks in one macromolecule would give us nucleic acid carriers of a new generation able not only to adsorb on cell membranes and stimulate endosomal uptake of oligonucleotides including small RNAs but also to induce permeabilization of endosomes and enable delivery of nucleic acids to the nucleus. We use oligonucleotides labeled with fluorescent dyes to study formation of their complexes with polymers. Our laboratory has equipments necessary to study oligonucleotides-polymer investigations in vitro, besides this some preliminary studies of these complexes penetration inside cells may be also performed.

Personnel involved in studies related to PROTHET's:

Marina  Gottikh. Leader Researcher - Head of the research team.

Nikolay S. Melik-Nubarov. Senior Researcher - Specialist in the polymer synthesis and permeability of lipid membranes. He has a great experience of studing polymers interactions with negatively charged polyanions including nucleic acids.

Irene D. Grozdova. Senior Researcher - Specialist in the drug delivery. She will study oligonucleotides-polymer complex penetration into cells.

Evgenii Zubin. Researcher - Specialist in the synthesis of modified oligonucleotides.

Julia K. Valeeva. Diploma student.

Recent Publications relevant to the project:

Gottikh M.B., Alekseev Y.I., Perminov A.V., Pinskaya M.D., Shabarova Z.A.: Oligodeoxyxylonucleotides Form Stable Triplexes with Single-Stranded DNA. Nuclesides & Nucleotides, 18, 1625-1627 (1999)

Helin V., Gottikh M., Mishal Z., Subra F., Malvy C., Lavignon M.: Cell cycle-dependent and specific inhibitory effect of vectorized oligonucleotides in cell culture. Biochemical Pharmacology, 58, 95-107 (1999)

Erukova V.Yu., Krylova O.O., Antonenko Yu.N., Melik-Nubarov N.S.: Effect of ethylene oxide and propylene oxide block copolymers on the permeability of bilayer lipid membranes to small solutes including doxorubicin. Biochim. Biophys. Acta, 1468, 73-86 (2000)

Maksimenko A.V., Volkov E.M., Bertrand J.-R., Porumb H., Malvy C., Shabarova Z.A., Gottikh M.B.: Targeting of single-stranded DNA and RNA containing adjacent pyrimidine and purine tracts by triple formation with circular and clamp oligonucleotides. Eur. J. Biochem., 267, 3592-3603 (2000)

Kozlova N.O., Bruskovskaya I.B., Okuneva I.B., Melik-Nubarov N.S., Yaroslavov A.A., Kabanov V.A., Menger F.M.: Interaction of a cationic polymer with negatively charged proteoliposomes. Biochim. Biophys. Acta, 1514 , 139-151 (2001)

Patent on the Ewing targeted antisense oligonucleotide:

A.V. Maksimenko, M.B. Gottikh, V. Helin, C. Malvy. Oligonucléotides stabilisés par une structure secondaire. Demande de brevet Bioalliance Pharma S.A., CNRS, IGR, Nø 99/02921 en date du 9/03/99