Problem Endometriosis is an inflammatory disease characterized by the endometrial-like tissue growth outside of the uterine cavity. This ectopic growth leads to hormonal imbalances, systemic inflammation, and debilitating pain during menstruation, sexual intercourse, and bodily functions . Although it affects 10–15% of reproductive age women, there is currently no cure and the diagnosis of this diseases remains a clinical challenge [1]. Current clinical management is limited to hormonal suppression, pain control and surgical excision [2]. Consequently, there is a critical need for non-invasive, targeted therapies that can modulate the immune response and minimize recurrence rates without compromising the patient’s reproductive health.
Endometriosis is an inflammatory disease characterized by the endometrial-like tissue growth outside of the uterine cavity. This ectopic growth leads to hormonal imbalances, systemic inflammation, and debilitating pain during menstruation, sexual intercourse, and bodily functions . Although it affects 10–15% of reproductive age women, there is currently no cure and the diagnosis of this diseases remains a clinical challenge [1]. Current clinical management is limited to hormonal suppression, pain control and surgical excision [2]. Consequently, there is a critical need for non-invasive, targeted therapies that can modulate the immune response and minimize recurrence rates without compromising the patient’s reproductive health.
Solution
I propose a single intraperitoneal dose of lipid nanoparticles administered at the close of laparoscopic surgery. In residual endometriotic cells overexpressing lncH19, a toehold switch activates expression of a bioPROTAC, an anti-STAT3 monobody fused to a VHL-based E3 ligase recruitment domain, driving targeted proteasomal degradation of STAT3, a key driver of endometriotic cell survival, invasion, and inflammation. Normal peritoneal tissue remains unaffected because the goal is to eliminate what the scalpel misses, before it has the chance to establish the disease again.
How does a toehold switch works?
How does a bioPROTAC works?
BioPROTAC (biological Proteolysis-Targeting Chimeras) are molecules capable of degrading target proteins by marking them for proteasomal degradation through the addition of polyubiquitin chains.
The mechanism functions by recruitment of an E3 ligase complex in close proximity of a target protein, which leads to target ubiquitination and subsequent proteasomal degradation.
The advantage of targeted protein degradation over traditional methods is that it can act on “undruggable” proteins, those lacking deep binding pockets or active sites that small-molecule inhibitors typically require.
They offer potential therapeutic applications in cancer, neuro
offering new avenues for treating diseases by precisely modulating protein levels and functions
Why LncRNA H19?
Why STAT3?
Bibliography
[1] M. Sahni and E. S. Day, “Nanotechnologies for the detection and treatment of endometriosis,” Front. Biomater. Sci., vol. 2, Nov. 2023, doi: 10.3389/fbiom.2023.1279358.
