Lipid-based nonviral vectors

Encapsulation of ohgonucleotides in delivery systems has been one the most promising strategies to overcome the described hindrances associated with their use in the free form. From the different delivery systems described to date, lipid-based nonviral vectors are among the best characterized delivery systems that may enable systemic... 

Despite the recent advances in the development of polymer-based nonviral vectors for siRNA or DNA delivery, the number of formulations that entered clinical trials has been substantially lower than lipid-based nonviral vectors. In this respect, the first-inhuman trial for siRNA delivery was a transferrin-targeted cyclodextrin, CALAA-01 (Fonseca et al., 2014). In 2008, Calando Pharmaceuticals (now part of Arrowhead Research Corporation) started a phase 1 clinical trial with CALAA-01 for the treatment of melanoma (Zuckerman et al., 2014). The rationale relied on the dowmegula-tion of ribonuclease reductase (RRM2) upon transferrin-mediated endocytosis of the siRNA-containing nanoparticle (Zuckerman et al., 2014). However, this nanoparticle was further withdrawn (Fonseca et al., 2014). 

Lipid- and polymer-based nonviral vectors for systemic siRNA and DNA delivery... 

Table 14.1 Current clinical trials using lipid- and polymer-based nonviral vectors containing siRNA (identification numbers of tbe clinical trial from bt s //clinicaltrials.gov/)... 

Among the several types of nonviral or synthetic vectors in use, cationic lipids have perhaps been the most widely studied to date. The reader is referred to recent reviews for additional information (5,6). Other cationic systems such as those based on cationic polymers, for example, poly-L-lysine and polyethyleneimine (PEI), share many of the properties of the cationic lipid systems, but they will not be described here. The reader is referred to recent reviews on... 

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