Inactivation of the gene will help with wound healing
Vanderbilt University researchers, working under the leadership of Dr. Craig Duvall, have developed a biodegradable framework for stable delivery of miRNAs that inactivate the expression of the PHD2 gene that suppresses the formation of new blood vessels.
Blood vessels deliver oxygen, nutrients and growth factors to the cells of damaged tissues. The results of earlier studies indicate that stimulation of angiogenesis – the formation of new vessels – contributes to faster wound healing.
One way to achieve the desired result is to introduce growth factors directly into the wound. However, many growth factors are required for the formation of blood vessels, and in order to ensure a full effect, their concentration and sequence of application must be strictly observed.
An alternative approach is to influence cells with small interfering RNAs (miRNAs) – short double-stranded RNA molecules with the ability to suppress the activity of the PHD2 gene. The result of inactivation of this gene is also an increase in the production of angiogenic factors, but this is achieved by triggering natural mechanisms that ensure the formation of mature full-fledged vessels.
However, until now, the delivery of the required amount of miRNA into cells has been an extremely difficult task, preventing the introduction of this approach into clinical practice.
The authors proposed a solution to this problem in the form of a biodegradable framework developed by them, which ensures the delivery of miRNA to the cells of surrounding tissues within a few weeks.
During the experiments, in order to ensure stable entry of miRNAs into cells, they were packed inside nanoparticles that provide protection from the action of extracellular matrix enzymes. Trehalose molecules were attached to the nanoparticles, after which they were injected into a skeleton implanted under the skin of mice. Trehalose acted as a material forming pores in the framework through which miRNA is released. The rate of release of therapeutic molecules can be changed by varying the number of trehalose molecules attached to nanoparticles.
Despite the fact that the dose of miRNA used in the experiments was 10-100 times lower than the doses used in earlier studies, 33 days after implantation of the skeleton, the density of blood vessels inside it was three times higher than the density of vessels in the surrounding tissue.
The microimage obtained with the help of computed tomography shows blood vessels formed inside the skeletons implanted under the mouse skin. The number of blood vessels in the blocked synthesis of the PHD2 protein (right) is 3 times greater than in the control.Dr. Duvall believes that the system developed by his group provides a unique opportunity to adapt the therapeutic use of miRNA to solve various clinical problems.
Depending on the target gene and the period of its expression during wound healing, by changing the rate of miRNA release, a rapid short-term or stable long-term effect can be achieved.
In the near future, the authors plan to test the effectiveness of the proposed approach on a rat model of diabetic ulcers and on other larger animal models. They are also going to explore the possibility of using the developed system to influence various genes to stimulate wound healing and treat other diseases.
Article by Christopher E. Nelson et al. Tunable Delivery of siRNA from a Biodegradable Scaffold to Promote Angiogenesis In Vivo is published in the journal Advanced Materials.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institute of Biomedical Imaging and Bioengineering: Breakthrough Technology Enables Gene Silencing to Heal Wounds.
Portal "Eternal youth" http://vechnayamolodost.ru22.01.2014