Gateway for:

Member Countries

Phospholipid Vesicles

#0889


Creation of Phospolipid Vesicles and Application in Non-Viral Transfection into Eucaryotic Cells for Gene Therapy

Tech Area / Field

  • BIO-CHM/Biochemistry/Biotechnology
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
18.03.1997

Leading Institute
State Research Institute of Organic Chemistry and Technology, Russia, Moscow

Supporting institutes

  • Institute of Biomedical Chemistry, Russia, Moscow

Project summary

Disturbances in genetic apparatus of cell-caused by defects of certain functional genes - as well as disturbances of control of gene expression are known to be associated with a variety of diseases. Gene therapy is aimed at replacing a defective gene or at the repairing of its structure. This approach is applicable in the control of hereditary diseases (such as Dushen's miodystrophy, cystic fibrosis) and infectious diseases (e.g. AIDS), in the therapy of tumors by use of the cytokine genes, in treatment of some neurological disorders and insulin-dependent diabetes.

The project proposed is aimed at development of technologies for preparing new lipids and phospholipids, as well as for creation, on their basis, of vesicles responsible for targeted delivery and for finding suitable conditions for non-viral transport of functional genes into eucaryotic cells by lipofection.

The phospholipid vesicles currently used in gene therapy for lipofection contain various cationic lipids. These are, for the most part, tertiary or quater-amines.

The project proposed is aimed at development of technologies for preparing new lipids and phospholipids, as well as for creation, on their basis, of vesicles responsible for targeted delivery and for finding suitable conditions for non-viral transport of functional genes into eucaryotic cells by lipofection.

The phospholipid vesicles currently used in gene therapy for lipofection contain various cationic lipids. These are, for the most part, tertiary or quaternary amines. However, many compounds used for these purposes have substantial disadvantages - i.e. bring about changes in the DNA secondary structure, elicit some toxic effects, etc. In view of this, the search of new cationic compounds and phospholipid compositions is a currently urgent problem. In this project, creation of targeted lipid vesicles will be undertaken, based on the synthesis of a series of (phospho) lipids having zwitter-ionic or cationic nature and characterized by varying ratios of the hydrophobic-to-hydrophilic moieties in their molecule, as well as with other structural changes: variable distances between charges, moieties, carbon chain branching, isomerism, introduction of oligosaccharides fragments, etc. It is supposed that syntheses of lipids and phospholipids of certain structure will make liposomes pH-sensitive, while endowing them with fusogenicity, target selectivity and all other required properties.

GosNIIOKhT is very experienced in studies on biologically active lipids and phospholipids, particularly - in syntheses of PAF (platelet activation factor) analogues and derivatives, in syntheses of phospholipid-nucleoside conjugates as potential anti-HIV agents - as well as in various other studies of such kind. The acquired experience may be applied, in the framework of the present project, to creation of organized (phospho) ipid surfaces (on liposomes/micelles) - for their subsequent transfection into cells using gene therapy technology. Thus, the project is in line with ISTC's activities on support of basic research for peaceful purposes and thus is designed to involve its scientists, earlier engaged in chemical weapons elaboration, into the international scientific community.

Transfection of functional genes into eucaryotic cells and the testing of their expression following lipofection will be carried out at the Institute of Biomedical Chemistry, in gene therapy laboratory - a pioneer of such studies in Russia. The laboratory will be concerned with selection and preparing plasmids containing functional genes, liposomal preparations and polynucleotide-lipid complexes, as well as with cell culturing and elucidation of transfection mechanisms.

The ultimate objective of these studies is to accomplish effective transfection of functional genes into normal and transformed eucaryotic cells with the use of liposomal / micellar vectors of original structure.


Back