Researchers at the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Engineering and Applied Sciences have identified ionizable lipid nanoparticles that can deliver mRNA in fetal therapy. The Proof of Concept is published in Science Advances.
Recent advances in DNA sequencing technology and prenatal diagnosis have made it possible to diagnose many genetic diseases before birth. Some of these are treated with protein replacement therapy or enzyme therapy after birth, but sometimes it is too late. The use of therapies while the patient is still in the womb holds the promise of being more effective in some conditions. The small size of the fetus allows the use of the maximum therapeutic dose, and its immune system may be more resistant to replacement therapy.
Of the potential carriers for introducing therapeutic protein substitution, mRNA differs from other nucleic acids such as DNA. The fact is that it does not need to penetrate the nucleus, and it can use the body’s own mechanisms to produce the desired proteins.
To identify potential non-viral delivery systems for therapeutic mRNA, the researchers developed a library of lipid nanoparticles less than 100 nanometers in size that efficiently enter the cells of mouse embryonic recipients. Each lipid nanoparticle formulation was used to encapsulate mRNA that was administered to fetal mice. Scientists have found that some lipid nanoparticles provide functional delivery of mRNA to the fetal liver. Some of them also deliver mRNA to the lungs and intestines of the fetus. Researchers evaluated the toxicity of lipid nanoparticles and concluded that they are safer than existing formulations.
The experiment results showed that lipid nanoparticles could provide a platform for the delivery of mRNA in the womb, which will be used in treatments such as fetal protein replacement and gene editing.