306-N16B

306-N16B is a lipidnanoparticle, and allows systemic codelivery of Cas9 mRNA and sgRNA. 306-N16B can transport mRNA to the pulmonaryendothelial cell. 306-N16B can be used for research of genome editing-based therapies. Based on the same lipid libraries with 306-O12B, the researchers also found that N-series ionizable lipids were able to selectively deliver mRNA to the lungs of mice. Compared with the liver-targeted O-series ionizable lipids which contained ester bond in lipid tail found in previous work, such as 306-O12B, the N-series ionizable lipids with
the lipid tail containing amide bond prefer to deliver mRNA to the lung. As a N-series ionizable lipid, the chemical structure of the 306-N16B is shown in Figure 4a, b. The difference of organ targeting may be due to their adsorption
of different protein coronas during blood circulation caused
by their different structures mentioned earlier.It has
shown that the second major protein of the protein
corona adsorbed by liver-targeting 306-O12B iLNPs was apolipoprotein
E (ApoE), while the three dominant proteins in the
protein corona adsorbed by lung-targeting 306-N16B iLNPs
were serum albumin, fibrinogen beta chain, and fibrinogen
gamma chain. However, the 306-N16B iLNPs showed less
organ selectivity when systematically codelivered Cas9
mRNA and sgRNA in vivo, which could simultaneously
activate tdTomato expression in the liver and lung of Ai14
mice, whereas single mRNA delivery could almost
exclusively deliver mRNA to the lungs. This surprising phenomenon
requires further investigation. Both the change of
iLNPs charge and the change of lipids functional group
can influence the distribution of iLNPs in vivo due to
the altering of protein corona composition. Therefore,
it is possible to control the organ targeting of iLNPs by
controlling the composition of the outer protein corona of
iLNPs.