Current Opinion in Molecular Therapeutics 

About: Current Opinion in Molecular Therapeutics is an academic journal. The journal publishes majorly in the area(s): Cancer & Genetic enhancement. It has an ISSN identifier of 1464-8431. Over the lifetime, 887 publications have been published receiving 25239 citations.

Shotgun proteomics: tools for the analysis of complex biological systems.

Abstract: Recent interest in proteomics has been fueled by the completion of multiple genome projects and ignited by the common need of biologists to rapidly and comprehensively evaluate complex samples of proteins on a global level. 'Shotgun proteomics' refers to the direct analysis of complex protein mixtures to rapidly generate a global profile of the protein complement within the mixture. This approach has been facilitated by the use of multidimensional protein identification technology (MudPIT), which incorporates multidimensional high-pressure liquid chromatography (LC/LC), tandem mass spectrometry (MS/MS) and database-searching algorithms. This review will focus on the most recent advances in methodologies for shotgun proteomics and address the limitations of the application of each to real biological samples.

Peptoids as potential therapeutics.

Abstract: Peptoids are oligomers of N-substituted glycine units. These molecules are almost perfectly suited for combinatorial approaches to drug discovery because large libraries can be synthesized easily from readily available primary amines. Moreover, major advances in screening methodology have allowed peptoid libraries of hundreds of thousands of compounds to be mined inexpensively and quickly for highly specific protein-binding molecules. These advances and the potential utility of peptoids as pharmacological agents are reviewed.

BiTE: Teaching antibodies to engage T-cells for cancer therapy.

Abstract: Bispecific T-cell-engager (BiTE) antibodies are designed to transiently engage cytotoxic T-cells for lysis of selected target cells. Although this therapeutic concept had been proposed more than two decades ago, BiTE, and also trispecific, antibodies did not achieve clinical proof-of-concept until the past 2 years. Their clinical activity corroborates findings that ex vivo expanded, autologous T-cells derived from tumor tissue, or transfected with specific T-cell receptors, have shown therapeutic potential in the treatment of solid tumors. While these personalized approaches prove that T-cells alone can have considerable therapeutic activity, even in late-stage cancer, they are cumbersome to perform on a broad basis. This is different for cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies, which facilitate generation of tumor-specific T-cell clones, and also for bi- and tri-specific antibodies that directly engage a large proportion of patients' T-cells for cancer cell lysis. The potential of global T-cell engagement for human cancer therapy by T-cell-engaging antibodies has yet to be fully investigated.

Adeno-associated virus vector integration.

Abstract: Adeno-associated virus (AAV) vectors efficiently transduce various cell types and can produce long-term expression of transgenes in vivo. Although AAV vector genomes can persist within cells as episomes, vector integration has been observed in various experimental settings, either at non-homologous sites where DNA damage may have occurred or by homologous recombination. In some cases, integration is essential for the therapeutic or experimental efficacy of AAV vectors. Recently, insertional mutagenesis resulting from the integration of AAV vectors was associated with tumorigenesis in mice, a consideration that may have relevance for certain clinical applications.

Locked nucleic acids: a promising molecular family for gene-function analysis and antisense drug development.

Abstract: Locked nucleic acids (LNAs) are a family of conformationally locked oligonucleotide analogs inducing unprecedented binding affinity towards DNA/RNA target sequences. Importantly, by virtue of the structural resemblance of LNAs to natural nucleic acid monomers, a combination of LNA chemistry with other oligonucleotide chemistries can be exploited to fine-tune the properties towards optimized antisense drug development and target validation technology. The first promising antisense results from experiments with LNA in living animals are described.