The liver is one of the primary sites for LNP accumulation because of the interaction between LNPs and the serum protein apolipoprotein E (ApoE), a protein that binds to the low-density lipoprotein receptor (LDLR) expressed in the liver.

The lungs are difficult to target with LNPs because of physiological factors that inherently favor other organs, like the liver and spleen. Accordingly, there is broad and current interest in the identification of ionizable cationic lipids that promote the distribution of LNPs to the lungs.

The spleen is an attractive target for LNPs targeting the immune system because of the large population of immune cells that reside in the spleen. However, it is a difficult organ to target because it must compete with the liver for LNP accumulation. Selection of ionizable lipids that target the spleen can aid in the distribution of LNPs to the spleen.

Because of the key role of lymph nodes in the function of the immune system, targeting LNPs to lymph nodes is an attractive strategy for immunological conditions and cancer.

Chimeric antigen receptor (CAR) T cell therapy is a promising strategy for cancer and immunological conditions. LNPs can be used to express the CAR that recognizes a specific antigen in T cells isolated from a patient ex vivo. When CAR T cells are adoptively transferred back into the patient, the CAR allows those T cells to identify and eliminate any cell expressing the antigen of interest

See our workflow for the delivery of mRNA to activated primary human T cells using C14-14 LNPs.

LNPs can enhance anti-tumor immunity by specifically targeting tumor cells, increasing the effectiveness of these therapies and avoiding off-target side effects.

Immune cells are attractive targets for therapies because of their direct role in the underlying biological mechanisms of many diseases. LNPs formulated with select ionizable lipids cationic lipids have been shown to specifically accumulate in immune cells, offering a potential pathway to these targeted therapies.

Messenger RNA (mRNA) is a single-stranded RNA that carries instructions for protein synthesis in the cytosol. It is used to induce target protein expression, making it a desirable strategy for diseases characterized by protein underexpression and/or functional deficiency, such as genetic diseases, or in vaccine development, by stimulating cells to produce beneficial proteins.

We compared four different LNP formulations for encapsulation efficiency and mRNA delivery in multiple cell types in vitro.

Small interfering RNA (siRNA) is a double-stranded RNA that inhibits mRNA translation, blocking protein synthesis. Accordingly, siRNA is a useful LNP cargo for targeting protein overexpression in disease.

CRISPR-Cas9 is a gene editing tool that permits the removal, addition, or alteration of a sequence in cellular DNA, allowing it to be useful for the correction of genetic disorders or in cell-based therapies like CAR T cell therapy.

Plasmid DNA (pDNA) carries therapeutic genes to human cells, where it must be transported into the nucleus. pDNA provides prolonged transgene protein expression, incorporating cell type-specific or inducible promoters, enhanced storage stability, and fewer limitations on cargo size.

We compared several LNP formulations for encapsulation and transfection efficiency of pDNA cargo in Huh7 and A549 cell lines.

Antisense oligonucleotides (ASOs) bind complementary RNA targets, inducing their degradation. Accordingly, they silence protein expression and are useful LNPs cargo for targeting protein overexpression in disease.

Self-amplifying RNA (saRNA) self-replicates upon cytosolic delivery, requiring less RNA cargo and promoting a long duration of protein expression, making it an intriguing approach for promoting longer lasting effects in novel LNP therapies.

Circular RNA (circRNA) is a single-stranded RNA with a circular structure, improving stability and promoting long duration of protein expression, making it an intriguing approach for promoting longer lasting effects in novel LNP therapies.