Many of today’s cancer treatments don’t sufficiently account for the individual nature of each instance of disease. Some forms of therapy, such as gene-silencing nucleic acids, are designed to target a very small number of disease-causing genes; however, the future of truly personalized treatment will need to account for the dynamism in molecular gene networks, and the variance in affected cell types between individuals.
By incorporating a robust biological methodology, researchers at Tel Aviv University–in collaboration with Integrated DNA Technologies and Harvard Medical School–aim to expand upon current treatments that target only a single cell receptor. To this end, they developed a flexible, self-assembling nucleic-acid delivery platform. Lead researcher Dan Peer, Ph.D., of the Laboratory of Precision Nanomedicine at Tel Aviv University’s School of Molecular Cell Biology and Biotechnology said that by utilizing biological affinity, this novel approach can be tailored to treat “an endless number of diseases.”
Current small interfering RNA (siRNA) delivery carriers target specific cells, and require chemical conjugation of the targeting agent. Peer said his method overcomes the limitations of today’s precision medicine by relying on a “linker”: a type of lipoprotein that binds to antibodies, altering them to create a delivery carrier capable of targeting various receptors. Linkers embedded in the nanoparticle membrane bind to a fixed region of any antibody of the same isotype, rendering chemical conjugation optimizations unnecessary. This allows a “theoretically unlimited selection” of specifically targeted carriers to safely pass and bind to cell surface receptors, according to Peer.
Study co-author Nuphar Vega believes their approach introduces a versatility to cell-specific gene therapy that may serve to bypass the expensive and unrealistic prospect of creating a drug carrier for every particular cell type or gene. “Rather, the focus should be on developing a nucleic acid-based tool to manipulate gene expression through a simple, constant exchange,” Vega said.
The carrier platform was implemented to treat symptoms of Inflammatory Bowel Disease in mice. Results showed that siRNA therapy “significantly and dramatically” reduced disease symptoms. Mice demonstrated “far less inflammation” following therapy, which suggests the therapy might have potential for treating IBD in human subjects, Peer said. Researchers also tested the platform’s ability to kill cancer cells in mice models with Mantle Cell Lymphoma, and found survival rates markedly improved as a result.
Peer believes the research could eventually be applied to treat a wide range of autoimmune diseases and cancer in humans. “It’s flexible enough to be easily customized to target any cell subset and to knock down any gene of choice. We think it has tremendous research and therapeutic potential,” Peer said of the siRNA delivery module.