Today : Jan 24, 2025
Science
24 January 2025

Breakthrough DNA Nano-Phage Technology Enhances Cellular Targeting

New method significantly improves specificity and efficiency of nanobody-mediated molecular computations for immunotherapy.

Researchers at Renji Hospital have made significant strides in improving cellular targeting techniques through the development of DNA nano-phage (DNP) technology. This innovative approach utilizes spatial segregation to facilitate advanced molecular computing processes involving nanobodies, enabling precise targeting of cell membrane receptors with minimal off-target effects.

Cell membrane receptors play pivotal roles in various biological processes, including cell proliferation, communication, and migration. Traditionally, targeting these receptors has posed substantial challenges, particularly when multiple cell types share similar receptors, leading to unintentional damage to healthy cells. To address this issue, the team introduced DNP, which not only enhances specificity but increases the effectiveness of immunotherapies.

The DNA nano-phage employs sophisticated constructions, encapsulating nanobodies within DNA cages to shield them from premature interactions with bystander cells. This unique internal computing layer is set to significantly advance the fields of targeted drug delivery and molecular imaging.

Through comprehensive kinetic models, the researchers could elucidate the impact of the cellular microenvironment on DNA computation processes. Notably, they uncovered the “diffusion trap” theory, explaining how rapid diffusion rates of DNA molecules can still lead to efficient computation; as DNA strands released within the cellular milieu frequently collide with cell membranes, this allows for binding before they can diffuse away.

Experimental results from the study showcasing DNP’s performance reveal its capability to successfully identify target cells even among complex mixtures, such as human blood samples, where it effectively blocked signals from unwanted erythrocytes. These findings represent considerable advancements compared to conventional methods, which often yield unsatisfactory specificity and biosafety outcomes.

By demonstrating DNP's capacity to facilitate enhanced phagocytosis of macrophages toward target cells through the blockade of CD47-SIRPα pathways without affecting surrounding tissue, the authors have opened new avenues for improved cancer immunotherapies.

“The proposed DNA nano-phage provides innovative solutions to complex challenges faced by current molecular targeting techniques,” the authors stated, highlighting the technology's vast potential.

These results have generated considerable excitement within the scientific community, as they may redefine how biomarkers and cell types can be selectively targeted. The study indicates future research directions focused on refining the DNP technology, potentially achieving even more accurate identification and manipulation of diseased cells, bolstering the effectiveness of precision medicine.

The findings are expected to pave the way for new treatments and significantly influence the fields of molecular biology, pharmacology, and immunotherapy.