CRISPRa-modified Adipocytes Can Significantly Inhibit Tumor Progression

In the field of cancer research, the unique metabolic mode of tumor cells has always been the focus of scientists. In order to meet the needs of their own rapid proliferation, tumor cells will try their best to absorb and metabolize a large amount of nutrients. They can reprogram metabolic pathways and prefer to obtain energy through aerobic glycolysis even when there is sufficient oxygen. This phenomenon is called the "Warburg effect". At the same time, in an oxygen-deficient environment, tumor cells will increase the use of lipids.

In response to these metabolic characteristics of tumor cells, researchers have tried a variety of methods to block their nutrient supply and inhibit tumor growth. For example, developing drugs targeting key targets of glycolysis and lipid metabolism, but these methods have certain limitations. Just as everyone is constantly exploring new treatment strategies, a study published in Nat Biotechnol, titled "Implantation of engineered adipocytes suppresses tumor progression in cancer models", brought new hope, namely adipose manipulation transplantation (AMT) technology.

AMT technology cleverly utilizes two characteristics of white adipose tissue. On the one hand, white adipose tissue can be easily obtained through liposuction and implanted into the body through surgery. On the other hand, it can be transformed into brown fat-like tissue in a specific way, a process called "browning". Using CRISPRa technology, researchers upregulated the expression of genes such as UCP1, PPARGC1A or PRDM16 in white adipocytes, successfully inducing browning of adipocytes, giving them stronger glucose and fatty acid uptake and metabolism capabilities.

The researchers verified the anti-cancer effect of AMT technology through a series of experiments. In in vitro experiments, CRISPRa-modified adipocytes were co-cultured with a variety of cancer cells (such as breast cancer, colon cancer, pancreatic cancer and prostate cancer cells). The proliferation of cancer cells was significantly inhibited, and the glucose uptake, glycolysis and fatty acid oxidation capabilities were also significantly reduced. This shows that the modified adipocytes are like "nutrient snatchers", taking away key nutrients from cancer cells, making the growth of cancer cells "unable to do what they want".

In animal experiments, the researchers constructed tumor xenograft models and genetic mouse models. In the xenograft model, UCP1-CRISPRa-modified human adipose organoids were co-transplanted with cancer cells into immunodeficient mice. It was found that the tumor volume was significantly reduced, while the expression of genes related to tumor proliferation, glycolysis, and fatty acid oxidation decreased, and hypoxia and angiogenesis were also improved. In genetic mouse models of pancreatic cancer and breast cancer, implantation of UCP1-CRISPRa-modified adipose organoids also effectively inhibited tumor development, reduced the expression of genes related to tumor metabolism and proliferation, reduced hypoxia and angiogenesis, and increased apoptosis of cancer cells.

More importantly, AMT technology has also shown great potential in clinical-related experiments. Adipocytes obtained from human breast tissue, after UCP1-CRISPRa treatment, can significantly inhibit tumor growth, whether co-cultured with breast cancer organoids in vitro or implanted into immunodeficient mice in vivo. In addition, AMT technology can also be regulated by inducible AAV vectors and cell scaffold systems to further improve the precision and effectiveness of treatment. The researchers also found that upregulating the expression of the UPP1 gene in adipocytes can inhibit the growth of uridine-dependent pancreatic ductal adenocarcinoma. This shows that AMT technology has the ability to provide personalized treatment for different cancer metabolic characteristics.

Figure 1. Implantation of Ucp1-CRISPRa adipose organoids in pancreatic and breast cancer genetic mouse models suppresses cancer development. (Nguyen H P, et al., 2025)

Overall, this study has opened up a new path for cancer treatment. AMT technology uses modified adipocytes to cleverly target cancer metabolic pathways and demonstrates strong tumor suppression capabilities. However, the technology is still in the research stage and may still be some distance away from clinical application. But it undoubtedly brings new hope to cancer patients.