Provided are compositions comprising an activatable proprotein comprising a first IL-15 or a variant thereof and a second IL-15Rα or variant thereof fused to a masking moiety comprising an antibody Fc region, and methods of using the same for cancer immunotherapy and other therapies.

Provided herein are combinations of an IL-2 molecule or mutein and a TNFR agonist, and complexes comprising IL-2/TNFR agonist molecules, such as Fc-bound IL-2/TNFR agonist molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Described herein are compositions, kits and methods for shredding the genomes of selected cell types, for example, the genomes of selected cancer cell types.

Compositions for CDKL5 gene therapy are provided, as well as recombinant CDKL5 proteins. Such CDKL5 gene therapy compositions and/or recombinant CDKL5 proteins may incorporate cell-penetrating polypeptides and/or leader signal polypeptides. Also provided are methods of producing such gene therapy compositions and recombinant CDKL5 proteins, as well as pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and recombinant CDKL5 proteins.

Provided are a calcium-sensing receptor (CaSR) agonist compound and application thereof. Specifically, provided are a series of polypeptide CaSR agonist compounds and pharmaceutically acceptable salts thereof, which have agonist effects on human CaSRs to reduce plasma parathyroid hormone and serum calcium ion levels, and can be used for treatment of metabolic diseases such as primary hyperparathyroidism, secondary hyperparathyroidism, and tumor-induced hypercalcemia.

In the various aspects and embodiments, this disclosure provides genetic, pharmacological, and mechanical stimuli for transitioning endothelial cells to hemogenic endothelial (HE) cells, and for transitioning HE cells to HSCs, including HSCs that comprise a significant level of LT-HSCs. The disclosure further provides methods for expanding HSCs using the genetic, pharmacological, and mechanical stimuli.

Fibronectin type III domains (FN3) that bind to serum albumin, related polynucleotides capable of encoding serum albumin-binding FN3 domains, cells expressing the FN3 domains, as well as associated vectors, detectably labeled FN3 domains and FN3 domains fused to a heterologous moiety are useful in extending the half-life of molecules in diagnostic and therapeutic applications.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

Provided is an improved cell-permeable nuclear import inhibitor (iCP-NI) for inhibition of cytokine storm or an inflammatory disease, in which solubility and stability are improved by introducing an advanced macromolecule transduction domain (aMTD)-based therapeuticmolecule systemic delivery technology (TSDT) into a cell-permeable nuclear import inhibitor (CP-NI, cSN50.1 peptide). The improved cell-permeable nuclear import inhibitor synthetic peptide according to the present disclosure more efficiently blocks signal transduction mediated by stress-responsive transcription factors (SRTFs) including NF-κB, based on remarkable cell permeability, and thus it may be used as an excellent prophylactic or therapeutic agent for cytokine storm or inflammatory diseases.