The starting point of this study stemmed from a clinical problem that left obstetricians and gynecologists deeply powerless. For patients with inherited ovarian gene mutations (such as BRCA1), clinical guidelines usually recommend prophylactic removal of both ovaries and fallopian tubes to eliminate cancer, but this means permanent infertility. Traditional gene therapy techniques, such as viral vectors, are considered no-go areas in extremely sensitive organs such as the ovaries, as they can be integrated into the germ cell genome and even interfere with the stability of the human gene pool if not properly operated. Even conventional oral or intravenous administration faces the dilemma of extremely low drug utilization efficiency and significant toxic side effects.

The surface of the ovaries is rugged and crisscrossed, and traditional electroporation devices cannot achieve "high conformal fit" on the surface of the organ, resulting in poor controllability and low efficiency of drug delivery, which cannot fundamentally be accurately treated and solve this kind of "forbidden area problem".

The team of Professor Chang Lingqian from the School of Medical Sciences and Engineering of Beihang University and the team of Professor Xu Ye from the School of Mechanical Engineering and Automation have taken a different path and obtained breakthrough inspiration from the ancient art of "paper-cutting". They creatively proposed the "conformal theory of customized paper-cutting for organs", and established the quantitative relationship between the geometric parameters of paper-cut structures, the curvature of organs, and material properties for the first time. By scanning the organ in 3D and intelligently generating the most suitable "coat" size, the team uses femtosecond laser technology to cut the device into interconnected and relatively independent "fragments", so that it can be delivered to the target organ location and assembled through microinterventional technology.

In the end, the effective coverage rate of this device called POCKET on the surfaces of different organs such as human ovaries, eyeballs, and kidneys can exceed 95%, just like putting on a tailor-made "electronic coat" for organs, overcoming the problem of "high conformity" and "high coverage".

Efficacy verification

This magical "electronic coat" is not just a well-fitting outerwear. It adopts a four-layer functional design that forms a precise spatial juxtaposition with the target cells through nanopore array films. When a low electric field is applied, the high-impedance nanopores produce a significant "nanoelectroporation" effect, reversibly and safely opening small pores on the cell membrane, while driving strong electrophoresis to increase the delivery speed of drugs or gene loads by nearly 1,000 times, thereby achieving efficient and safe intracellular delivery.

The efficacy of this technique has been strongly validated in a variety of animal models. In a mouse model simulating human BRCA1 mutations, POCKET successfully delivered functional BRCA1-Plasmid into whole ovarian surface cells (OSEs). This not only reduces the incidence of cancer in mice to zero in one treatment cycle, but also stimulates cells to secrete exosomes carrying relevant mRNA, effectively improving the symptoms of premature ovarian failure. More importantly, the hormone secretion function, egg quality and fertility of the ovaries are restored, and the offspring produced are healthy. This result provides women with oncogene mutations with a new option to prevent cancer and preserve fertility without removing the ovaries.

Content source: Beihang University,China Science Daily‌