5 results about "Unfolded protein response" patented technology

The present invention provides a multiomics approach, which integrate single-cell RNA-sequencing (scRNA-seq) and spatiotemporal transcriptomics (ST) offering potential for dissecting transcriptional networks and revealing cell-cell interactions involved in biomolecular pathomechanisms. The present invention also provides a multimodal approach combining high-throughput scRNA-seq and ST to elucidate XLRS-specific transcriptomic signatures in two XLRS-like models with retinal splitting phenotypes, including genetically engineered (Rs1emR209C) mice and patient-derived retinal organoids harboring the same patient-specific p.R209C mutation. Through multiomics transcriptomic analysis, the endoplasmic reticulum (ER) stress / eIF2 signaling, mTOR pathway, and the regulation of eIF4 and p70S6K pathways as chronically enriched and highly conserved disease pathways between two XLRS-like models are identified. Western blots and proteomics analysis validated the occurrence of unfolded protein responses, chronic eIF2α signaling activation, and chronic ER stress-induced apoptosis. Furthermore, therapeutic targeting of the chronic ER stress / eIF2α pathway activation synergistically enhanced the efficacy of AAV mediated RS1 gene delivery, ultimately improving bipolar cell integrity, postsynaptic transmission, disorganized retinal architecture and electrophysiological responses. Collectively, the complex transcriptomic signatures obtained from Rs1emR209C mice and patient-derived retinal organoids using the multiomics approach provide opportunities to unravel potential therapeutic targets for incurable retinal diseases, such as XLRS.

The present invention provides methods for treating conditions, diseases or disorders associated with sex hormone imbalance and specifically with a low sex hormone level or response using NAP peptide, specifically conditions, diseases or disorders mediated via unfolded protein response.

The present invention relates to the use of a regulatory nucleic acid sequences that are able to regulate gene expression in eukaryotic cells and which are responsive to the unfolded protein response (UPR). There are disclosed regulatable introns and UPR-inducible promoters, which are able to regulate gene expression. There are also disclosed recombinant expression constructs comprising such regulatory nucleic acid sequences, whereby expression of the encoded expression product can be induced by invoking the unfolded protein response (UPR) in a eukaryotic cell containing the construct, methods of using such constructs and associated vectors, cells and suchlike.

The present technology provides a combination approach for treating multidrug resistant cancer. Multidrug resistant cancers have more mitochondrial networks than drug sensitive cancers. A first agent fragments mitochondrial networks, dissociates mitochondria from the endoplasmic reticulum, and lower the threshold for apoptosis. A second active agent induces the unfolded protein response, causing stress to the endoplasmic reticulum and limiting the ability of multidrug resistant cancer cells to grow and survive. A third active agent directly activates mitochondrial apoptosis, leading to death of the cancer cells. The active agents can be combined into a nanoparticle formulation for simultaneous delivery into multidrug resistant cancer cells. The formulation serves as a nanomedicine for treatment of multidrug resistant cancers such as multidrug resistant triple negative breast cancer.

The invention discloses siRNA for treating UMOD gene mutant autosomal dominant hereditary renal tubular interstitial nephropathy, and belongs to the field of biomedicine. The siRNA comprises a positive-sense strand and an antisense strand, and the nucleotide sequences of the positive-sense strand and the antisense strand are SEQ ID NO.1 and SEQ ID NO.2 respectively. Compared with the prior art, the UMOD point mutation mouse model is successfully constructed, and the model completely simulates typical disease phenotypes of ADTKD-UMOD patients. In-vivo and in-vitro functional verification shows that Umod mutated mice and cell models can activate unfolded protein reaction and cell ferroptosis and apoptosis for the first time. The invention further adopts targeted UMOD mRNA for intervention by using siUMOD, and the result shows that siRNA can inhibit Umod mutant cell ferroptosis and cell apoptosis, relieve endoplasmic reticulum stress caused by mutation, improve mouse renal function and delay disease progression at the same time. According to the application, an innovative and feasible method is provided for treatment of ADTKD-UMOD, and a universal platform technology is provided for single-gene hereditary nephropathy.