Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or...
Patent
1998-10-02
2000-12-26
Yucel, Remy
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
530350, C12N 700
Patent
active
061657727
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to a vehicle for the transport of molecular substance, such as DNA, RNA, protein, PNA, pharmaceuticals of lipophilic and lipophobic character, into eukaryotic cells. The invention furthermore relates to a process for the preparation of the vehicle, its use and compositions of agents for applying or carrying out the invention.
Under certain conditions, eukaryotic cells absorb DNA, proteins and other molecules. The absorption rate, however, is usually low. Additionally, the transport of the molecular substance is not predeterminable with respect to the nature of the cells and the cell compartment or the site in the intracellular region.
In order to improve, in particular, the absorption of DNA into eukaryotic cells, it is known to use viral vectors as vehicles for transport into the cell. The use of viral vectors is disadvantageous because in this case the cotransfection of viral genomes can occur.
It is furthermore disclosed in U.S. Pat. No. 4,950,599 to lock molecular substance such as DNA into eukaryotic cells using empty virus capsids, in particular polyoma capsids. Even in this process cotransfection of viral genomes cannot be excluded. Additionally, molecules whose size exceed the internal volume of the polyoma capsid cannot be packed therein. Finally, synthetic preparation of polyoma capsids, which comes into consideration as one possibility of avoiding cotransfection, is extremely difficult and cost-intensive.
The object of the invention is to eliminate the disadvantages of the prior art, in particular to indicate a vehicle for the transport of molecular substance into eukaryotic cells which can be used universally and can be prepared simply and in a cost-effective manner.
This object is achieved by the features of claim 1. Advantageous embodiments of the invention are clear from the features of claims 2-15.
SUMMARY OF THE INVENTION
According to the invention, a vehicle is provided which contains at least one capsomere derived or originating from a virus, which on one of its sides has a structure interacting with the molecular substance such that the molecular substance can be bound or added to the capsomere.
The vehicle according to the invention has the advantage that it can be synthetically prepared relatively simply. Cotransfection of viral genomes can thus be avoided. Additionally, because of the provision of the structure interacting with the molecular substance, molecular substance of any size can be bound and locked into cells. To do this, the typical capsid form no longer has to be maintained. Using the vehicles according to the invention, besides capsomeres protective forms of a different kind are also formed. A particular advantage of the invention can be seen in that, with the vehicle according to the invention, depending on the formation of the at least one capsomere, it is possible to transport the molecular substance specifically into certain cells and/or to a prespecified site in the intracellular region.
The capsomere is preferably formed such that it is suitable for the construction of a capsid or a capsid-like structure. It is particularly advantageous if the capsomere spontaneously forms capsids.
According to a further embodying feature of the invention, the capsomere is derived from the polyoma virus, it being possible to form it from the VP1 pentamer of the polyoma virus.
Alternatively, the capsomere can be obtained from "non-enveloped" viruses such as DNA-containing Papovaviridae, in particular polyoma viruses and the papilloma viruses, Iridoviridae, Adenoviridae, Parvoviridae or RNA-containing Picornaviridae, in particular polio viruses, Caliciviridae, Reoviridae and Birnaviridae, or derived therefrom. Depending on the type of molecular substance to be transported, it may also be advantageous to obtain the capsomere from the outer and/or inner coat of "enveloped" viruses such as DNA-containing Poxviridae, Herpesviridae, Hepadnaviridae or RNA-containing Retroviridae, Paramyxoviridae, Sendai viruses, Orthomyxoviridae, Bunyavi
REFERENCES:
patent: 4950599 (1990-08-01), Bertling
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