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A new strategy for the treatment of viral infections

Wolf, Markus

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Abstract

Intact viruses, containing no viral genome but which are loaded with a therapeutic drug or virus like particles loaded with antiviral drugs are potentially selective drug carriers for the intracellular delivery of therapeutics. These virus constructs could be used as therapeutics for the therapy of viral infections. For example HI-viruses could be designed, that are loaded with antisense oligonucleotides that avoid replication of the wild type HI virus. The advantage of such antisense oligonucleotide loaded viruses could be the fact that they enter cells and deliver the therapeutics to the host cells of the wild type HI virus. It should be possible to treat all viral infections with this method. Wild type viruses are therapied by a modified virus of the same type or a virus like particle containing a antiviral drug – e.g. an antisense oligonucleotide. This method should work for all viruses. Additionally, a new method is described how intact viruses, containing no viral genome but which are loaded with a therapeutic drug could be obtained. The major obstacle is that the viral genome and viral proteins must be present for virus assembly on the one hand, on the other hand it must be removed subsequent to virus assembly in order to obtain a safe drug carrier. The idea is: Virus assembly takes place in the presence of the viral genome with subsequent removal of the viral genome. Firstly the viral genome is immobilized on a solid support – comparable to DNA chips. Virus assembly proceeds at the solid support. After virus assembly and drug loading the immobilized viral genome is removed. Viral proteins could be obtained from a packaging cell line. The lysate of such a packaging cell line containing the viral proteins is incubated with the immobilized viral genome to allow virus assembly. The lysate is removed after succesful assembly. The next step would be the loading of the virus with a therapeutic drug. As the viral proteins contain amino and carboxy groups they can be chemically modified by a therapeutic drug. Finally the drug loaded virus is removed from the solid support and with it from the viral genome. This could be a strategy to obtain drug loaded, intact viruses lacking the viral genome.

Translation of abstract (English)

Das Ziel dieses Forschungsvorhabens besteht darin, Nukleinsäure freie, intakte Viren zu gewinnen, die statt des viralen Genoms Arzneistoffe oder therapeutische Proteine enthalten. Diese Arzneistoff enthaltenden Viren sollen als hochspezifische Träger für den intrazellulären Transport von Arzneistoffen dienen. Um den Zusammenbau intakter, Nukleinsäure freier Viren und die Inkorperation der Arzneistoffe zu ermöglichen, muss zunächst das virale Genom auf einem Träger – vergleichbar mit DNA Chips - immobilisiert werden. Nachfolgend wird das immobilisierte Genom mit dem Lysat einer Verpackungszellinie, welches die Hüllproteine des Virus enthält, inkubiert. Auf diese Weise werden intakte Viren an dem immobiliserten Träger zusammengesetzt. Nachfolgend wird das immobiliserte, virale Erbgut durch Abwaschen von den gewünschte, den Wirkstoff enthaltenden Viren abgetrennt. Die viren sollen statt der viralen DNA mit antiviralen Wirkstoffen beladen werden. Da die Viren die gleiche Bioverteilung wie die Krankheits erregenden Wildtypviren haben, gelangen die Arzneistoff beladenen Viren in potentielle Wirtszellen. Damit wäre eine Therapie mit dem gleichen Virustyp möglich, der die Infektion verursacht. Viren sollen also als antivirale Arzneiträger verwendet werden.

Item Type: Article
Date Deposited: 30 Jun 2006 10:55
Date: 2006
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Subjects: 610 Medical sciences Medicine
Controlled Keywords: Virostatikum, Virusinaktivierung
Uncontrolled Keywords: antiviralvirus like particles , new antiviral therapy
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