49 results about "Pro-Apoptotic Proteins" patented technology

Undifferentiated primordial stem cells are manipulated to permit their long term growth in defined media lacking serum and feeder layer cells by shifting the apoptotic balance of the cells, through increasing the activity of Bcl-2 family anti-apoptotic proteins or decreasing the activity of Bcl-2 family pro-apoptotic proteins. In some embodiments of the invention, the Bcl family protein is Bcl-2. The ES cells sustain the characteristics of undifferentiated, pluripotent stem cells during long-term serum- and feeder layer cell-free conditions, including the ability to be expanded in vitro, but maintain their potential to differentiate into mature cell types.

The present invention relates to targeted killing of a cell utilizing a chimeric polypeptide comprising a cell-specific targeting moiety and a signal transduction pathway factor. In a preferred embodiment, the signal transduction pathway factor is an apoptosis-inducing factor, such as granzyme B, granzyme A, or Bax.

Single-domain anti-bodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the active of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and / or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins.

An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and / or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and / or Bax serve as improved immunogens and tumor immunotherapeutic agents.

Provided nucleic acid- based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell thatis associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and / or eliminating the growth and / or survival of a cell, such as a senescent cell and / or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression constructfor the target cell-specific, production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a targetcell that is a senescent cell or a cancer cell.

Nucleic acid compositions encoding a pro-apoptotic protein, Bok (Bcl-2-related ovarian killer) are identified. Bok has conserved Bcl-2 homology domains 1, 2 and 3 and a C-terminal transmembrane region present in other Bcl-2 related proteins, but lacks the BH4 domain found only in anti-apoptotic Bcl-2 proteins. Over-expression of Bok induces apoptosis. Cell killing induced by Bok is suppressed by co-expression with selective anti-apoptotic Bcl-2 proteins. Bok is highly expressed in the ovary, testis and uterus, particularly in granulosa cells, the cell type that undergoes apoptosis during follicle atresia. Identification of Bok as a new pro-apoptotic protein with wide tissue distribution and hetero-dimerization properties facilitates elucidation of apoptosis mechanisms in reproductive and other tissues, and provides a means for manipulating apoptosis.

The invention relates to treatment of autoimmune diseases, and particularly discloses compositions for treatment of autoimmune diseases or conditions that result in hair loss, such as alopecia. The compositions include first and second polynucleotides, wherein a) the first polynucleotide comprises a sequence encoding an autoantigen or an antigenic fragment thereof, with at least about 50% of CpG dinucleotide of the first polynucleotide being methylated; and b) the second polynucleotide comprises a sequence encoding a pro-apoptotic protein, or a functional pro-apoptotic fragment thereof, with the pro-apoptotic protein being selected from a group consisting of BAK, BAX, BIM, a death receptor 4, a death receptor 5 or a FAS receptor, wherein 15% or less of said CpG dinucleotide of the second polynucleotide is methylated. The compositions are used intradermally for inducing a tolerogenic immune response against said autoantigen.