Packaging and Release of mRNA and of other Macromolecules from Supramolecular Virus-Like Assemblies

 Four-component Ionizable Lipid Nanoparticle (LNP) for mRNA vaccines

Four-component Ionizable Lipid Nanoparticle (LNP) for mRNA vaccines

One-component Sequence-Defined IAJD Dendrimersome Nanoparticle (DNP)

One-component Sequence-Defined IAJD Dendrimersome Nanoparticle (DNP)

Targeted Delivery of Luc-mRNA of the Sequence-Defined IAJD DNPs

Targeted Delivery of Luc-mRNA of the Sequence-Defined IAJD DNPs

We developed one-component, sequence-defined Ionizable Amphiphilic Janus Dendrimers (IAJDs) and their assemblies with mRNA. These Dendrimersome Nanoparticles (DNPs) were investigated for the delivery of mRNA for vaccines and nanotherapeutics. The DNPs have the potential to make less expensive, more stable, and easily stored vaccines against viruses compared to the current 4-component Lipid Nanoparticles, LNPs. We have shown that the structural design of the IAJD molecules allows the formation of DNPs that selectively deliver Luc-mRNA to the lung, liver, spleen, and lymph nodes. Simplifying the IAJD structure allows us to change the delivery from lung to liver and spleen. The DNPs elaborated in this work are excellent candidates for more efficient and less expensive vaccines than the current ones.

The three JACS papers referenced below received support from this effort.   Penn has filed patent applications on work described in the references.

(1) J. Am. Chem. Soc., 2021, 143, 12315–12327.
(2) J. Am. Chem. Soc., 2021, 143, 17975–17982.
(3) J. Am. Chem. Soc., 2022, 144, 4746–4753.

 

Broader Impact

High School Teacher Daaiyah White from Mastery Charter Schools was supported by this grant to participate in this research. We also welcomed Hayley Neubauer, a chemistry undergraduate student at Gettysburg College and Isis P. Carmona-Sepúlveda, an undergraduate student from Puerto Rico, as REU summer interns in summer 2021. The last two undergraduate students subsequently became graduate students in chemistry.

NSF-REU Employees and Undergraduates

High School Teacher

Daaiyah White portrait

Daaiyah White
Science & Technology Instructional Leader & Teacher

 

Undergraduate Students

Hayley Neubauer portrait

Hayley Neubauer
Recently graduated with a Bachelor of Science in Chemistry

Isis P Carmona-Sepulveda portrait

Isis P. Carmona-Sepúlveda
Now graduate student at Penn State University