Precise, Efficient Delivery of mRNA Medicine to the Placenta

Using tiny lipid nanoparticles (LNPs) to improve mRNA medicine delivery and uptake in the placenta for healthier pregnancies
Problem:
The placenta is an important biological barrier that connects the mother and fetus while keeping their blood supplies separate, enabling nutrient and oxygen delivery and waste removal for healthy development. Abnormal development, such as in pre-eclampsia, can create serious health risks for both mother and baby during pregnancy. With no current existing cure, researchers are exploring lipid nanoparticles (LNPs) to deliver mRNA as a potential therapy. However, organ-specific LNP delivery requires modifying LNP properties like size, charge, stiffness, and stability, which influence efficacy and uptake. For treating developmental disorders like pre-eclampsia, there is a need for engineering LNP design for targeted delivery to placental cells.
Solution:
The authors developed a set of LNPs with varying elasticity for specific mRNA delivery to the placenta. These LNPs were formulated with either cholesterol or cholesterol analogs like campesterol, β-sitosterol, or stigmasterol. These LNPs demonstrated improved mRNA delivery to the placenta in pregnant mice.
Technology:
The researchers created the LNPs as four component systems by combining an ionizable lipid that was previously identified for mRNA delivery to the placenta, as well as components like phospholipid, a cholesterol or cholesterol analog, and lipid-anchored polyethylene glycol (PEG) in a microfluidic device. The use of cholesterol and cholesterol analogs can change the elastic properties of LNPs, thus improving mRNA delivery to the placenta.
Advantages:

Allows specific delivery of LNPs directly into the placenta with increased delivery of mRNA
Enables precise tuning of LNP elasticity through cholesterol analog incorporation
Allows significantly increased uptake of mRNA in placental trophoblast cells

Stage of Development:

Preclinical Discovery

<rss.caption
Schematic of Modified LNPs and Properties (a) Schematic of LNP synthesis via phase mixing (b) Schematic of tunable LNP elasticity through cholesterol analog incorporation (c) In vivo imaging system (IVIS) imaging images showing luciferase mRNA delivery to the placenta and fetus (d,e) Quantification of LNP-delivered luciferase mRNA in placentas and fetuses
Intellectual Property: