Biological approach to precision medicine targets many diseases


A Palestinian worker arranges bottles to be filled with alcohol at a pharmaceutical drug manufacturi

Medicine (illustrative).
(photo credit: AP)

The complexity of cancer and other diseases demands a more powerful arsenal of therapies than what is currently available. Most therapeutic approaches ignore the dynamic molecular network of genes, targeting only very few selected disease-related genes.

A new Tel Aviv University study published in Nature Nanotechnology proposes a novel approach to manipulate genes using a self-assembling platform that delivers nucleic acids, such as small interfering RNAs (siRNAs), to distinct subsets of cells. While current practices of precision medicine target a single cellular receptor, the new modular platform offers a better biological approach that may hold the key to the future of personalized medicine, said Prof. Dan Peer of the laboratory of precision nanomedicine at the School of Molecular Cell Biology and Biotechnology, who led the research.

The researchers are currently interested in advancing a proof-of-concept in humans.

“The siRNA delivery-targeted carriers constructed today hone in on specific cells and require chemical conjugation of the targeting agent,” said Peer. “The new platform is based on biological affinity, a self-assembling approach that can be translated to target an endless number of diseases and conditions.”

Research for the study was conducted by first co-authors Dr. Ranit Kedmi and Nuphar Veiga and colleagues at Peer’s lab, with others from TAU’s Veterinary Service Center and Boston.

The new platform “removes many of the hurdles” plaguing precision medicine today, Peer said. At the heart of the delivery platform is the “linker,” a lipoprotein that binds to the antibody common region. Since all antibodies of the same family share a common region, a simple alteration of the antibody results in a novel delivery carrier that adjusts to the target receptor of choice.

“Because its construction relies on affinity interactions, there’s no need to introduce chemical conjugation optimizations for the method to function,” noted Peer. “Linkers are stuck in the nanoparticle membrane and bind to a fixed region of any antibody of the same isotype. This affords safe passage to a theoretically unlimited selection of carriers targeting distinct cell surface receptors.”

“We believe this modular delivery platform serves as a milestone that renders precision medicine truly feasible,” added Veiga.

For the research, the scientists used the platform to target colon macrophages in order to reduce inflammatory symptoms caused by Inflammatory Bowel Disease (IBD) in mouse models. The mice exhibited far less inflammation, which suggests the possibility of promising new IBD therapeutic opportunities, Peer said.

“Our delivery platform can be adjusted for each patient to target a potentially endless number of receptors. 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.”

Omega 3 from fish for cancer prevention

Omega 3 derived from fish provides a more powerful punch than flaxseed and other oils when it comes to cancer prevention, according to a first-ever study at the University of Guelph in Ontario, Canada. Human health and nutritional sciences Prof. David Ma has discovered that marine-based omega-3 is eight times more effective at inhibiting tumor development and growth.

“This study is the first to compare the cancer-fighting potency of plant-derived versus marine-derived omega 3 on breast tumor development,” said Ma. “There is evidence that both omega 3 from plants and marine sources are protective against cancer, and we wanted to determine which form is more effective.”

There are three types of omega 3 fatty acids: a-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA is plant-based and found in such edible seeds as flaxseed and in oils, such as soy, canola and hemp oil. EPA and DHA are found in marine life, such as fish, algae and phytoplankton.

Published in the Journal of Nutritional Biochemistry, the researchers fed the different types of omega 3 to mice who had a highly aggressive form of human breast cancer called HER-2. This form affects a quarter of women with breast cancer, giving patients a poor prognosis.

“The mice were exposed to the different types of omega 3 even before tumors developed, which allowed us to compare how effective the fatty acids are at prevention,” he explained. “It’s known that EPA and DHA can inhibit breast tumor growth, but no one has looked directly at how effective these different types of omega 3 are compared to ALA.”

Ma found that overall exposure to marine-based omega 3 reduced the size of the tumors by 60% to 70% and the number of tumors by 30%.

However, higher doses of the plant-based fatty acid were required to deliver the same impact as the marinebased omega 3. Omega 3 prevents and fight cancer by turning on genes associated with the immune system and blocking tumor growth pathways, said Ma.

“It seems EPA and DHA are more effective at this. In North America, we don’t get enough omega 3 from seafood, so there lies an opportunity to improve our diet and help prevent the risk of breast cancer.”

Based on the doses given in the study, Ma said humans should consume two to three servings of fish a week to have the same effect.

Besides certain foods containing EPA and DHA, supplements and functional foods, such as omega 3 eggs or DHA milk, can offer similar cancer prevention effects. The next step is to investigate the effects of omega 3 on other forms of breast cancer.




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