Drug delivery system based on responses to an HIV infectious signal

Daisuke Asai, Kota Bae Kodama, Yoko Shoji, Hideaki Nakashima, Kenji Kawamura, Jun Oishi, Masanori Kuramoto, Takuro Niidome, Yoshiki Katayama

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Gene therapy is a growing topic in the medical arena. Since the safety system of gene therapy has not been sufficiently established, its clinical use is limited. Recently, we developed a cell-specific gene regulation system based on a new concept, D-RECS, or Drug and Gene Delivery System Responding to Cellular Signals. We hoped here to apply this D-RECS concept to gene therapy for virus infections. In the present study, we report the design, synthesis and characterization of the functional polymers, which are able to discriminate normal and human immunodeficiency virus type 1 (HIV-1) infected cells. In the D-RECS concept, certain intracellular signals, which are extraordinary activated in the target disease cells specifically, are used as a trigger to activate a transgene expression. Thus, we paid attention to HIV protease as a target signal in this case, because HIV protease is essential for the proliferation of HIV. This protease is therefore an indicator of HIV infection. Two types of polymers were designed and synthesized using methacryloyl peptide and acrylamide with radical copolymerization as a functional gene regulator. The grafted peptide possesses a cationic protein transduction domain (PTD) sequence of HIV-Tat protein, GRKKRRQRRRPPQ for cell permeation, which are connected with polyacrylamide backbone via a consensus substrate sequence for HIV protease, SQNY/PIVQ. At first, the polymers were evaluated to see whether they possess DNA binding ability and HIV protease responsibility using gel retardation assay. The results suggested that a polymer could form a stable complex with DNA and release the DNA specifically responding to HIV protease activity. Furthermore, it was shown that this controlled release of DNA by the HIV protease signal-responsive intelligent polymer actually regulated the gene expression in the cell-free system. This system would be a useful tool for gene therapy in HIV infection, and this methodology will be applicable if the cationic peptide is replaced by another virus-specific protease, which is critical for the replication of a corresponding virus.

Original languageEnglish
Pages (from-to)386-391
Number of pages6
JournalMedicinal Chemistry
Volume4
Issue number4
DOIs
Publication statusPublished - Aug 28 2008

Fingerprint

HIV Protease
Drug Delivery Systems
HIV
Polymers
Genetic Therapy
DNA
Peptides
HIV Infections
Peptide Hydrolases
Human Immunodeficiency Virus tat Gene Products
Viruses
Gene Transfer Techniques
Cell-Free System
Acrylamide
Consensus Sequence
Electrophoretic Mobility Shift Assay
Virus Diseases
Regulator Genes
Transgenes
HIV-1

All Science Journal Classification (ASJC) codes

  • Drug Discovery

Cite this

Asai, D., Kodama, K. B., Shoji, Y., Nakashima, H., Kawamura, K., Oishi, J., ... Katayama, Y. (2008). Drug delivery system based on responses to an HIV infectious signal. Medicinal Chemistry, 4(4), 386-391. https://doi.org/10.2174/157340608784872307

Drug delivery system based on responses to an HIV infectious signal. / Asai, Daisuke; Kodama, Kota Bae; Shoji, Yoko; Nakashima, Hideaki; Kawamura, Kenji; Oishi, Jun; Kuramoto, Masanori; Niidome, Takuro; Katayama, Yoshiki.

In: Medicinal Chemistry, Vol. 4, No. 4, 28.08.2008, p. 386-391.

Research output: Contribution to journalArticle

Asai, D, Kodama, KB, Shoji, Y, Nakashima, H, Kawamura, K, Oishi, J, Kuramoto, M, Niidome, T & Katayama, Y 2008, 'Drug delivery system based on responses to an HIV infectious signal', Medicinal Chemistry, vol. 4, no. 4, pp. 386-391. https://doi.org/10.2174/157340608784872307
Asai D, Kodama KB, Shoji Y, Nakashima H, Kawamura K, Oishi J et al. Drug delivery system based on responses to an HIV infectious signal. Medicinal Chemistry. 2008 Aug 28;4(4):386-391. https://doi.org/10.2174/157340608784872307
Asai, Daisuke ; Kodama, Kota Bae ; Shoji, Yoko ; Nakashima, Hideaki ; Kawamura, Kenji ; Oishi, Jun ; Kuramoto, Masanori ; Niidome, Takuro ; Katayama, Yoshiki. / Drug delivery system based on responses to an HIV infectious signal. In: Medicinal Chemistry. 2008 ; Vol. 4, No. 4. pp. 386-391.
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