Abstract: A dental article such as a dental tray aligner or a dental crown that includes a substrate including a polymeric material having a modulus of elasticity that reduces upon exposure to water and a water-resistant coating on the substrate, where the water-resistant coating comprises parylene. In some examples, the water-resistant coating may include one or more layers that include parylene.

Abstract: The invention provides methods for selective targeting of live cells, which have undergone or are undergoing radiation or chemotherapy, at a site of interest with a cell-penetrating polypeptide. In one embodiment of the invention, the method comprises contacting the live cells with a cell-penetrating polypeptide comprising cell-penetrating determinants so that the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith such that the complex or associated polypeptide-DNA so bound bind the live cells and penetrates the live cells thereby selectively targeting live cells at a site of interest with a cell-penetrating polypeptide.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: Compositions and methods of treating autoimmune diseases by administering a subject in need thereof an effective amount of an inhibitor of the importin pathway are also provided. Typically, the autoimmune disease has one or more symptoms or pathologies dependent on or otherwise caused by nuclear penetrating antibodies, for example, nuclear penetrating autoantibodies. In specific embodiments, the autoimmune disease is scleroderma or a form of lupus, for example systemic lupus erythematosus. In preferred embodiments, the inhibitor of the importin pathway is a macrocyclic lactone such as an avermectin or a milbemycin. Compositions, formulations, and dosage forms including an effective amount of the macrocyclic lactones to reduce nuclear localization of a nuclear penetrating antibody are also provided. The compositions can be employed in the disclosed methods. Exemplary dosages ranges and dosage regimens are also provided.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: Amino acid sequences capable of enhancing nuclear translocation are provided. Also referred to a nuclear localization signals (NLS) the sequences can be linked to or grafted into antibodies or fragments or fusion proteins thereof to enhance nuclear translocation of the antibody. Compositions and antibodies including an NLS conjugated or otherwise linked directly or indirectly to an active agent cargo are also provided. Exemplary cargo includes proteins, peptides, carbohydrates, polysaccharides, nucleic acid molecules, inorganic molecules, organic molecules, and diagnostic agents. Pharmaceutical compositions further including a pharmaceutically acceptable carrier are also provided. Methods of delivering the composition or antibody alone or with a cargo linked thereto to the nucleus of cell, methods of selecting or screening for compositions having a desired cellular activity, and methods of treating diseases and disorders are also provided.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78 or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78 or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.

Abstract: Antigen binding molecules that bind to the epitope of 3E10, and methods of use thereof are provided. The antigen binding molecule can include, for example, two or more variant single chain variable fragments (scFv) of monoclonal antibody 3E10, wherein the variant scFv has one or more insertions, deletions, or substitutions relative to a corresponding 3E10 scFv, and wherein the molecule can bind, preferably specifically bind, to the epitope of 3E10. Methods of using the antigen binding molecules for treating cancer and viral infections or preventing viral infections are also provided.

Abstract: The invention provides methods for selective targeting of live cells, which have undergone or are undergoing radiation or chemotherapy, at a site of interest with a cell-penetrating polypeptide. In one embodiment of the invention, the method comprises contacting the live cells with a cell-penetrating polypeptide comprising cell-penetrating determinants so that the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith such that the complex or associated polypeptide-DNA so bound bind the live cells and penetrates the live cells thereby selectively targeting live cells at a site of interest with a cell-penetrating polypeptide.

Abstract: Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies.

Abstract: Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies.

Abstract: It has been established that cancer cells with oncogenic mutants in the small GTPase K-Ras are susceptible to antibodies that bind intracellular guanosine, but delivery of antibodies into cells can be challenging. A subset of lupus autoantibodies is associated with anti-guanosine activity, and is capable of cellular penetration. These antibodies have potential as therapeutic agents targeted towards K-Ras associated malignancies.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78 or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: Antigen binding molecules that bind to the epitope of 3E10, and methods of use thereof are provided. The antigen binding molecule can include, for example, two or more variant single chain variable fragments (scFv) of monoclonal antibody 3E10, wherein the variant scFv has one or more insertions, deletions, or substitutions relative to a corresponding 3E10 scFv, and wherein the molecule can bind, preferably specifically bind, to the epitope of 3E10. Methods of using the antigen binding molecules for treating cancer and viral infections or preventing viral infections are also provided.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: It has been established that cancer cells with oncogenic mutants in the small GTPase K-Ras are susceptible to antibodies that bind intracellular guanosine, but delivery of antibodies into cells can be challenging. A subset of lupus autoantibodies is associated with anti-guanosine activity, and is capable of cellular penetration. These antibodies have potential as therapeutic agents targeted towards K-Ras associated malignancies.

Abstract: Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.