(Nanowork News) Inspired by the design of the space shuttle, Penn Engineering researchers have invented a new method to synthesize key components of lipid nanoparticles (LNPs), an innovative delivery vehicle for mRNA therapeutics, including the Pfizer-BioNTech and Moderna COVID-19 vaccines. Manufacturing LNPs while increasing the efficacy of mRNA delivery to cells for medicinal purposes.
In one paper Nature Communications (“In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors”), Michael J. Mitchell, associate professor of bioengineering, presents a new method for synthesizing ionizable lipidoids, the key chemical components of LNPs. explains. It helps protect and deliver the medicinal payload. In the paper, Mitchell and his co-authors tested mRNA drug delivery for the treatment of obesity and gene editing tools for the treatment of genetic diseases.
Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA into cells, but methods to produce these molecules are time- and cost-intensive. “We provide a novel compositional strategy for the rapid and cost-effective synthesis of these lipidoids,” said Xuexiang Han, a postdoctoral student in the Mitchell Lab and co-author of the paper.
The method involves combining three chemicals: an amine “head,” two alkyl epoxide “tails,” and finally two acyl chloride “branched tails.” It is no coincidence that the finished lipidoid resembles a space shuttle strapped to two booster rockets. Mr. Han recalls watching a documentary about the space shuttle during his college days and being impressed by the design of the solid rocket boosters that allowed the space shuttle to enter orbit. “I thought we could add two branch tails as ‘boosters’ to the lipidoid to promote delivery of the mRNA,” Han said.
Indeed, the addition of the branched tail significantly increased the ability of the new lipidoid-loaded LNPs to deliver mRNA to target cells. It's similar to a rocket that uses boosters to penetrate the atmosphere more easily.
“After delivering mRNA using these lipidoids, we saw a dramatic increase in hormones that regulate metabolism to target cells,” Mitchell said. “This is really exciting to consider as a treatment option for obesity.”