The fourth international CDDR (Centre for Drug Delivery Research) conference was held at the School of Pharmacy, University of London, UK in December last year (Organisers: Gregory Gregoriadis and Alexander Florence, School of Pharmacy). The purpose of this meeting was to cover recent progress and trends in the use of liposomes (and other lipid-based systems) in drug and vaccine delivery and targeting. Topics covered included cancer treatment, lipoplex assembly and structure, DNA vaccines, and lipid-based vaccines. The presentations related to gene therapy are discussed in this brief report.
Several groups discussed the delivery of antisense oligonucleotides (AS-ODN) encapsulated in cationic liposomes. Rahman and co-workers (Georgetown University, Washington, DC, USA) presented a study where AS-ODN were used to inhibit Raf-1 protein expression in the relatively radioresistant laryngeal squamous carcinoma cell line SQ-20B. Raf-1 is a protein kinase important in cell growth, proliferation and survival. Its overexpression or activation is associated with in vitro resistance. In vitro data showed 13% uptake of an AS-ODN against the translation initiator region (ATG-ODN) over 24 h and there was a 10-fold advantage over free ODN when encapsulated in liposomes. Raf-1 protein expression was inhibited with the maximal effect at 8 h. In a SQ-20B tumour model, delivery of ATG-ODN resulted in a reduction in tumour volume to one third the size of the control group after 60 days. The combination of AS-ODN and ionising radiation led to significant tumour regression. This was due to apoptosis. Ponzoni and co-workers (Giannina Gaslinin Institute, Italy) discussed the application of AS-ODNs to treat advanced stage neuroblastoma. AS-ODNs targeted to the c-myb oncogene were encapsulated in long-circulating anti-GD2-targeted immunoliposomes. Uptake into human NB cells in vitro was specific with a four- to five-fold increase in AS-ODN uptake in GD2-positive cells compared with GD2-negative cells. Also, this uptake was five to 10 higher compared with free AS-ODN or AS-ODN encapsulated in non-targeted liposomes. Reduced levels of c-myb protein were noted and complete inhibition of cell proliferation.
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