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InteRNA, Collaborators Publish Details of siRNA, microRNA Delivery Technology

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NEW YORK (GenomeWeb) – InteRNA Technologies and academic collaborators this month reported details of an siRNA-delivery technology capable of specifically targeting tumor vasculature, along with in vitro data demonstrating its ability to carry siRNAs into human umbilical vein endothelial cells (HUVECs).

The technology is currently being developed by InteRNA to deliver antiangiogenic microRNA mimics for the treatment of cancer, according to a company official.

Blocking the formation of new blood vessels has long been a key therapeutic strategy for cancer, and endothelial cells, along with vascular endothelial growth factor (VEGF), are known to be crucial for the angiogenesis. As such, VEGF has been a popular cancer target, including for those working in the RNA medicines space, yet the delivery of nucleic acids has remained a challenge.

To address this issue, InteRNA researchers and colleagues at Utrecht University and Free University Medical Center in Amsterdam looked to anionic lipoplexes functionalized with a 33-mer angiostatic peptide called anginex.

First described in a 2001 paper, anginex has been shown by a number of groups to inhibit vascular endothelial cell proliferation and induce apoptosis, to specifically target tumor vasculature, and to use galectin-1 — a lactoside-binding lectin involved in cancer — as its cellular receptor.

In a paper appearing this month in the International Journal of Pharmaceutics, the InteRNA team described the preparation of anginex lipoplexes, dubbed Angiplex, encapsulating siRNAs targeting VEGF receptor 2. These particles had an average size of 120 nanometers and a net negative charge.

In culture, they demonstrated low cellular toxicity and high cell internalization into HUVECs that resulted in up to 61 percent target knockdown. Notably, the lipoplex also led to an intrinsic downregulation of VEGFR-2 irrespective of its therapeutic payload or targeting ligand — a phenomenon that the study's authors are presently investigating.

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