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DNA encoding the prostate-specific membrane antigen-like gene and uses thereof

a prostate-specific membrane antigen and gene technology, applied in the field of cell biology, can solve the problems of limited value of psa, inability to identify prior art, and inability to provide patients with options, and achieve the effect of inhibiting cell death

Inactive Publication Date: 2005-03-24
SLOAN KETTERING INST FOR CANCER RES
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes ways to stop cells from dying by blocking certain genes or proteins that cause damage. This can help researchers better study how different parts of the body work together to prevent disease.

Problems solved by technology

The technical problem addressed in this patent text is the need for a better marker to diagnose and treat prostate cancer. The current biomarker, prostate specific antigen (PSA), has limitations in its effectiveness and is not specific enough to target the disease. The prostate specific membrane antigen (PSMA) is a promising marker, but its expression is also found in other tissues and is related to a gene called PSMA-like. The invention aims to distinguish between the two genes and their respective protein products to improve the accuracy of diagnosis and treatment.

Method used

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  • DNA encoding the prostate-specific membrane antigen-like gene and uses thereof
  • DNA encoding the prostate-specific membrane antigen-like gene and uses thereof
  • DNA encoding the prostate-specific membrane antigen-like gene and uses thereof

Examples

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example 1

[0069] Differentiating the PSMA Gene from the PSMA-Like Gene

[0070] To map the human PSMA gene and resolve the controversy regarding its true location (11p versus 11q), a number of primer pairs were designed with homology to various regions of the PSMA gene, including introns. These primers were then used to amplify DNA from the NIGMS somatic cell hybrid mapping panel which consists of a hybrid containing chromosome 11, one containing chromosome 11p, one containing 11q and a hamster parental line. While the amplified regions of exon 16, intron n-o (primers used correspond to nt 54278-54536 in the PSMA genomic sequence and encompass exon 15 of the PSMA gene) and intron 6 are found on both chromosome 11p and 11q, the promoter region of the PSMA gene is only amplified from the hybrid containing chromosome 11p (see FIG. 1). The fact that intron sequences are present also confirms that the gene on chromosome 11q is not a pseudogene, but in fact, a gene duplication.

[0071] Intron-based pr...

example 2

[0073] Evidence for a Novel PSMA Splice Variant

[0074] As analysis of the brain and prostate PSMA and PSMA-like genes was being carried out, RT-PCR of the terminal region of the PSMA gene detected an alternate splice form of PSMA present in LNCaP cells and normal prostate that is not present in normal brain (see FIG. 3). This appears to be a novel splice variant of PSMA and the expression pattern of this variant is evaluated in prostate and other tissues.

example 3

[0075] Screening for Ligands of PSMA / PSM′

[0076] It has previously been reported that mitochondrial aspartate-aminotransferase (mAAST) binds to PSMA, since it co-elutes with PSMA from affinity columns made with the 7E11C5.3 antibody [27]. Using a similar isolation method, co-elution with PSMA of a protein of the size expected for mAAST from LNCaP cells was demonstrated. However, this protein is apparently not a PSMA ligand, as it is also eluted from the same 7E11C5.3 affinity column that has been treated with protein lysate from non-PSMA expressing PC3 cells.

[0077] The yeast-two-hybrid system is also being used to screen for PSMA ligands. To date, six million clones have been screened from a prostate library and six different, consistently interacting clones have been identified. Significantly, one of the positive clones corresponds to Survivin, a recently cloned apoptosis inhibitor which is highly expressed in prostate tumors, but is not typically expressed in terminally differenti...

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Abstract

The present invention discloses a new gene, termed PSMA-like, that is very similar to the prostate-specific membrane antigen (PSMA) gene and cross-reacts with current detection methods for PSMA. The present invention also provides for a method of distinguishing the PSMA and PSMA-like mRNAs and/or proteins for diagnostic and therapeutic strategies that desire specific targeting of either the PSMA or PSMA-like gene.

Description

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Claims

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Application Information

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Owner SLOAN KETTERING INST FOR CANCER RES
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