Non-transgenic crop improvement via cis-regulatory editing is limited by rare activating alleles and incomplete promoter maps. A massively parallel reporter assay in sorghum protoplasts quantifies more than 30,000 CRISPR-mimicking variants across three photosynthesis genes, finely mapping cis-regulatory modules and pinpointing compact edits that drive upregulated protein production.

Immune cell engagers (ICEs) have emerged as a promising strategy for cancer immunotherapy, but their efficacy in solid tumors remains limited, partly as a result of the difficulty of coordinating activating and inhibitory signals within the same immune cell. Here, we report a logic-gated cis-targeting strategy that enables ICEs to coordinate activating and inhibitory signals within macrophages, thereby enhancing tumor clearance in mouse models of solid cancers.

This Review discusses the promises and pitfalls of biological AI algorithms and presents a vision for generalist biological artificial intelligence, in which models can perform diverse tasks across biological domains.

An engineered Escherichia coli Nissle 1917 strain carrying a synthetic arginine–nitric oxide (NO) circuit enables sustained intratumoral NO production that promotes vascular normalization and immune reprogramming. This reshaped tumor microenvironment synergizes with blockade of the immune checkpoint PD-L1 to reinvigorate CD8⁺ T cells and drive durable tumor regression in mouse models.