Figure 3.

Delivery of a transgene to primate brain and peripheral organs and the effect of tissue-specific promoters on gene expression.

A plasmid DNA encoding the lacZ gene under the influence of either the widely expressed SV40 promoter (A–I) or the eye-specific promoter derived from the 5′ flanking sequence (FS) of the opsin gene (J–N) was encapsulated in human insulin receptor (HIR) monoclonal antibody (MAb) targeted lipid nanoparticles (LNPs) and injected intravenously in the adult rhesus monkey at a plasmid DNA dose of 12 μg/kg. Organs were removed at 48 h and lacZ gene expression was detected by X-gal histochemistry. (A) Coronal section of primate brain removed 48 h after LNP administration shows global expression of the SV40-lacZ transgene throughout the primate brain. (B,C,D) Light microscopy of the specific regions of the primate brain shows SV40-lacZ gene expression in the choroid plexus (B), the columns of the occipital cortex (C), and the cerebellum (D). The SV40-lacZ transgene is also expressed in the monkey eye (E), cerebrum (F), cerebellum (G), liver (H), and spleen (I). Conversely, the opsin-lacZ transgene is expressed only in the primate eye (J) and there is no expression of the opsin-lacZ in the monkey cerebrum (K), cerebellum (L), liver (M), or spleen (N). (A–I) reproduced from [19], CC BY 4.0 license. (J–N) reproduced from [66], CC BY NC ND 3.0 license.