Berkeley's Innovative Genomics Institute Uses CRISPR to Boost Sorghum Photosynthesis Gene Expression More Than 30-Fold
Two companion Nature Biotechnology papers map over 30,000 CRISPR edits across sorghum's regulatory DNA, achieving unprecedented control over photosynthesis genes with implications for crop yields and carbon capture.
Overview
Scientists at the Innovative Genomics Institute (IGI) at UC Berkeley have published two companion papers in Nature Biotechnology demonstrating a massively parallel CRISPR editing platform that can tune the expression of photosynthesis genes in sorghum by more than 30-fold. The research represents the first time scientists have been able to systematically map and control gene expression across an entire crop promoter region at this scale, moving CRISPR-based agriculture beyond simple gene knockouts toward precise regulatory fine-tuning.
Sorghum is a drought-resilient C4 cereal crop grown across 42 million hectares worldwide, valued both as a food staple in sub-Saharan Africa and as a bioenergy feedstock. Enhancing its photosynthetic efficiency could simultaneously improve yields and increase the amount of atmospheric carbon dioxide the crop absorbs.
What We Know
The two studies, published as companion papers in Nature Biotechnology, developed a primary cell-based massively parallel reporter assay (MPRA) in sorghum leaf cells. The platform tested more than 30,000 mutations, including deletions, substitutions, and motif insertions, across the promoters and five-prime untranslated regions of three rate-limiting photosynthesis genes: PsbS, Raf1, and SBPase.
Each of these genes plays a distinct role in the photosynthetic machinery. PsbS encodes a protein central to nonphotochemical quenching, the process by which plants dissipate excess light energy. Previous transgenic overexpression of PsbS in rice, soybean, and tobacco has been shown to improve light harvesting and agronomic yield. Raf1 encodes a molecular chaperone for the Rubisco enzyme, the most abundant protein on Earth and the primary gateway for atmospheric carbon fixation. SBPase is a core enzyme in the Calvin-Benson cycle whose expression limits the regeneration of Rubisco’s substrate, according to Nature Biotechnology.
The researchers found that gene expression was most tunable within a roughly 500-base-pair core promoter region. Within these regions, they identified compact deletions and motif insertions that increased protein production by more than 30-fold relative to wild type, outperforming conventional transgenic enhancer elements, according to Nature Biotechnology.
The work was supported in part by an $11 million grant from the Chan Zuckerberg Initiative, which in 2022 funded IGI’s broader effort to use CRISPR for enhancing carbon capture through plants and soil microbes. The initiative is led by IGI founder and Nobel laureate Jennifer Doudna, alongside researchers including Krishna Niyogi, Peggy Lemaux, and Myeong-Je Cho, according to UC Berkeley.
The IGI team estimates that expanding sorghum cultivation combined with improved photosynthetic efficiency could capture up to 1.4 billion metric tons of CO2 equivalent annually worldwide, according to UC Berkeley.
What We Don’t Know
The published results come from cell-based assays in sorghum leaf tissue, not from whole-plant field trials. Whether a 30-fold increase in promoter-driven reporter expression translates proportionally to improved photosynthetic rates, biomass accumulation, or grain yield in field conditions remains untested. Gene expression changes in isolated cells do not always predict outcomes in complex multicellular organisms subject to environmental variability.
The studies focused on three photosynthesis genes, but photosynthesis involves hundreds of proteins operating in concert. Boosting individual components could create bottlenecks elsewhere in the pathway or trigger regulatory feedback loops that blunt the gains observed in isolated assays.
It is also unclear how quickly these edits could move through regulatory pipelines. Gene-edited crops face varying oversight depending on jurisdiction. In the United States, the USDA has exempted certain CRISPR edits that mimic natural mutations from regulatory review, but edits involving insertions of novel motifs may face a longer path to approval.
The timeline for translating these laboratory results into commercially available improved sorghum varieties has not been specified by the researchers.
Analysis
The significance of this work lies less in the specific fold-change numbers and more in the methodological advance. Until now, CRISPR applications in crops have largely focused on knocking out undesirable genes, such as those conferring disease susceptibility or producing allergens. The ability to systematically dial gene expression up or down by editing regulatory DNA, rather than the protein-coding sequence itself, opens a fundamentally different approach to crop improvement.
The choice of sorghum as the target crop is strategically significant. As a C4 plant, sorghum already possesses a more efficient carbon-concentrating mechanism than C3 staples like rice and wheat. If the regulatory editing platform proves transferable to other crops, as the researchers suggest it should, the approach could be applied to less photosynthetically efficient species where the marginal gains would be larger.
The carbon capture dimension adds a dual rationale. Agricultural land already covers roughly 1.5 billion hectares globally. If even modest photosynthetic efficiency gains could be achieved across a fraction of that area, the cumulative impact on atmospheric CO2 removal could be material, without requiring new land use or infrastructure.