摘要:
Dominant negative (DN) variants of transcriptional enhancer factor 1-related (RTEF-1) are described. DN RTEF-1 polypeptides may be directly targeted to cells or delivered in nucleic acid expression vectors to alter cellular transcription. Methods for inhibiting VEGF production and thereby treating angiogenic disorders such as cancer are described. For example, in certain aspects, DN RTEF-1 may be used to treat angiogenic disorders of the eye such as age related macular degeneration (AMD).
摘要:
Dominant negative (DN) variants of transcriptional enhancer factor 1-related (RTEF-1) are described. DN RTEF-1 polypeptides may be directly targeted to cells or delivered in nucleic acid expression vectors to alter cellular transcription. Methods for inhibiting VEGF production and thereby treating angiogenic disorders such as cancer are described. For example, in certain aspects, DN RTEF-1 may be used to treat angiogenic disorders of the eye such as age related macular degeneration (AMD).
摘要:
The human soluble neuropilin-1 (sNRP) polyadenylation signal (sNRP-poly(A)), situated downstream of the GT splice donor site of intron 12 of the full-length neuropilin-1 gene, also functions as the termination codon for sNRP. This 17 nucleotide sequence efficiently facilitates addition of poly(A) tails to RNAs expressed in cells. The present invention shows that this optimally succinct sequence has similar activity to the SV40 polyadenylation signal that is currently used in expression vectors. By using this shorter dual termination/polyadenylation signal and avoiding the need for large and cumbersome polyadenylation signals, expression vectors may be engineered to carry considerably larger genes.
摘要:
The present invention provides lentiviral vectors that are useful in human gene therapy for inherited or acquired proliferative ocular disease. It furnishes methods to exploit the ability of lentiviral vectors to transduce both mitotically active and inactive cells so that eye diseases may be treated.
摘要:
Disclosed are variant RTEF-1 polypeptides having an RTEF-1 amino acid sequence with one or more internal deletions, wherein the polypeptides reduce VEGF promoter activity. Some of the RTEF-1 polypeptides include an amino acid sequence that is at least 80% identical to the contiguous amino acids of 1) amino acids 24 to 47 of SEQ ID NO:15 and 2) each of SEQ ID NOs:16 and 17, but does not comprise the contiguous amino acids of SEQ ID NOs:8, 9, 11, or 12. Also disclosed are nucleic acids encoding the variant RTEF-1 polypeptides of the present invention. Pharmaceutical compositions that include the polypeptides and nucleic acids of the present invention are also disclosed. Methods of inducing cell contact inhibition, regulating organ size, and reducing intracellular YAP activity are also set forth, as well as methods of treating hyperproliferative diseases such as cancer using the pharmaceutical compositions of the present invention.
摘要翻译:公开了具有一个或多个内部缺失的RTEF-1氨基酸序列的变体RTEF-1多肽,其中多肽降低VEGF启动子活性。 一些RTEF-1多肽包括与SEQ ID NO:15的1)氨基酸24至47和2)SEQ ID NO:16和17各自的连续氨基酸至少80%相同的氨基酸序列 但不包含SEQ ID NO:8,9,11或12的连续氨基酸。还公开了编码本发明变体RTEF-1多肽的核酸。 还公开了包括本发明的多肽和核酸的药物组合物。 还提出诱导细胞接触抑制,调节器官大小和减少细胞内YAP活性的方法,以及使用本发明的药物组合物治疗过度增殖性疾病如癌症的方法。
摘要:
The present invention provides lentiviral vectors that are useful in human gene therapy for inherited or acquired proliferative ocular disease. It furnishes methods to exploit the ability of lentiviral vectors to transduce both mitotically active and inactive cells so that eye diseases may be treated.
摘要:
Disclosed are recombinant polypeptides that include (a) a filaggrin amino acid sequence and (b) a cell importation signal sequence that includes a motif of two to fifteen amino acids, wherein the motif includes at least one arginine residue and at least one methionine residue. Also disclosed are nucleic acids encoding the recombinant polypeptides of the present invention, and compositions that include the recombinant polypeptides and nucleic acids of the present invention. Methods of treating or preventing a skin disease or skin disorder using the compositions of the present invention are also included, as well as kits that include a sealed containing that includes a recombinant polypeptide of the present invention.
摘要:
Disclosed are variant RTEF-1 polypeptides having an RTEF-1 amino acid sequence with one or more internal deletions, wherein the polypeptides reduce VEGF promoter activity. Some of the RTEF-1 polypeptides include an amino acid sequence that is at least 80% identical to the contiguous amino acids of 1) amino acids 24 to 47 of SEQ ID NO:15 and 2) each of SEQ ID NOs:16 and 17, but does not comprise the contiguous amino acids of SEQ ID NOs:8, 9, 11, or 12. Also disclosed are nucleic acids encoding the variant RTEF-1 polypeptides of the present invention. Pharmaceutical compositions that include the polypeptides and nucleic acids of the present invention are also disclosed. Methods of inducing cell contact inhibition, regulating organ size, and reducing intracellular YAP activity are also set forth, as well as methods of treating hyperproliferative diseases such as cancer using the pharmaceutical compositions of the present invention.
摘要翻译:公开了具有一个或多个内部缺失的RTEF-1氨基酸序列的变体RTEF-1多肽,其中多肽降低VEGF启动子活性。 一些RTEF-1多肽包括与SEQ ID NO:15的1)氨基酸24至47和2)SEQ ID NO:16和17各自的连续氨基酸至少80%相同的氨基酸序列 但不包含SEQ ID NO:8,9,11或12的连续氨基酸。还公开了编码本发明变体RTEF-1多肽的核酸。 还公开了包括本发明的多肽和核酸的药物组合物。 还提出诱导细胞接触抑制,调节器官大小和减少细胞内YAP活性的方法,以及使用本发明的药物组合物治疗过度增殖性疾病如癌症的方法。
摘要:
The present invention provides lentiviral vectors that are useful in human gene therapy for inherited or acquired proliferative ocular disease. It furnishes methods to exploit the ability of lentiviral vectors to transduce both mitotically active and inactive cells so that eye diseases may be treated.
摘要:
The human soluble neuropilin-1 (sNRP) polyadenylation signal (sNRP-poly(A)), situated downstream of the GT splice donor site of intron 12 of the full-length neuropilin-1 gene, also functions as the termination codon for sNRP. This 17 nucleotide sequence efficiently facilitates addition of poly(A) tails to RNAs expressed in cells. The present invention shows that this optimally succinct sequence has similar activity to the SV40 polyadenylation signal that is currently used in expression vectors. By using this shorter dual termination/polyadenylation signal and avoiding the need for large and cumbersome polyadenylation signals, expression vectors may be engineered to carry considerably larger genes.