Precise RNA expression, tailored to specific brain regions, cell types, and subcellular compartments, is pivotal for orchestrating complex brain functions. In the first part of my talk, I will introduce a confocal imaging-based spatial transcriptomics platform, STARmap, that seamlessly combines in situ hybridization, hydrogel tissue chemistry, and in situ sequencing technologies. Leveraging scalable experimental and computational pipelines, we have constructed a comprehensive spatial cell atlas of the mouse brain, revealing subregion-specific cell types, previously undiscovered tissue architectures, and viral tropisms. The second part of my talk transits to chemical modifications on messenger RNAs (mRNAs) and their far-reaching implications in gene expression regulation and the development of RNA therapeutics. I will discuss the messenger-oligonucleotide conjugate RNAs (mocRNAs) design, showcasing how we can harness chemical modifications for engineering enhanced gene delivery vectors. Looking into the future, I aim to innovate and integrate chemical and spatial profiling approaches to understand tissue health and disease in-depth.