Given the recent sequencing of the human genome, we have entered into a new era of medicine, “Genome Medicine,” that transcends our traditional notion of pharmacology and drug therapies. We now have the potential to address the genetic root of disease pathology, either by identifying and modifying the function of the gene product responsible for a given pathology through pharmacological means, or by directly modifying the gene with gene therapy. However, as is the case with most new pharmacological treatments, gene therapy has encountered numerous challenges that have limited its efficacy in both preclinical and clinical situations. Some of these ... Read more

Gene therapy is recognized as a promising approach for the treatment of serious diseases including monogenic diseases, infectious diseases, and cancer. Conventional vectors used for delivering therapeutic genes are virus-based vectors, such as the adenovirus, retrovirus, lentivirus, and adeno-associated virus. Since these viruses can infect a wide range of tissues, it is essential to be able to deliver these viruses specifically to the target tissues in vivo. If these viruses are administrated intravenously, the genes will be introduced into unexpected tissues, such as those around the injected place, causing side effects. These situations also make the repetitive administration of genes ... Read more

In immune responses, externally acquired antigens such as those from bacteria are processed by antigen-presenting cells and presented in the complex with MHC II (major histocompatibility complex class II) to CD4+ T cells. Activation of CD4+ cells leads to cell-mediated inflammatory responses and B cell activation/antibody production. Internally synthesized antigens in antigen-presenting cells such as viral proteins form complexes with MHC I molecules. These complexes activate CD8+ cytotoxic T cells and lead to the destruction of virus-infested cells.

The DNA vaccine, or as it is sometimes referred to a genetic vaccine, is a new generation of vaccines. Different from the traditional ... Read more

Antibodies are key tools in proteomics. Their high specificity and affinity allow them to be used to measure individual proteins in complex mixtures, and most importantly to provide quantitative information. There is now great interest in generating proteome-wide sets of antibodies in order to discover biomarkers of disease and to enhance drug development. Antibodies are traditionally produced by injecting a pure form of the protein mixed with an adjuvant into an animal. The pure protein is usually produced either by overexpression in a host such as E. coli and purifying it using a fused tag (e.g., GST, 6-histidines), or by ... Read more

In the past few years, many studies have suggested that alternative splicing is a widespread mechanism of functional regulation in the human genome. Cancer-associated splice variants have also been reported for genes such as EGFR, CD44, and recently many others (Xu et al., 2003). High throughput genomics data, such as those obtained from EST (expressed sequence tag) sequencing, have provided a major new opportunity for discovering cancer-specific alterations in splicing (Wang et al., 2003). Over 4 million human ESTs have been sequenced, and most can be classified both by their tissue of origin and whether they were derived from a ... Read more

We recently published our work constructing lentiviral vectors (LV) to consistently express two genes simultaneously or independently (Yu et al., 2003). In a separate study, we reported efficient gene transfer to human T lymphocytes while retaining the T cell functionality and antigen repertoire (Zhou et al., 2003).

Recombinant vectors based on retroviruses (including both onco-retroviruses and lentiviruses) remain the only choice to efficiently and stably transduce primary mammalian cells. Compared to onco-retroviral vectors (RVs), which have been the mainstay for stable gene delivery in the past 20 years, LVs offer several advantages. First, LVs can transduce both dividing and non-dividing cells ... Read more

The search for alternative treatments for congestive heart failure remains an ongoing venture. Exciting research over the last 2 years has changed the long held dogma that the heart cannot regenerate itself. The work of many groups can be summarized by the following concept: increasing the number of CD117+ (c-kit+) stem cells in cardiac tissue or in the coronary circulation within 2 days of a myocardial infarction results in regeneration of myocardial tissue and improved cardiac function.

Animal studies by Orlic, Anversa and colleagues have demonstrated that either the direct injection of bone marrow-derived CD117+ stem cells in the infarct border ... Read more

Cell-free systems for the expression of proteins are widely used in basic and clinical research. In molecular diagnostics, the method is used for the detection of mutations in a variety of disease-related genes that lead to premature translation termination caused by nonsense substitutions or frameshift mutations. The use of in vitro transcription and translation (IVTT) assays for population-wide disease screening demands the development of nonisotopic, automatable, and sensitive assay systems. Several recent papers have begun to address these issues (Traverso et al., 2003; Gite et al., 2003; Kahmann et al., 2002). All approaches are based on the protein truncation test, ... Read more

Autoreactive T cells are part of the normal immune system and are kept under control by mechanisms known as anergy. Autoimmune diseases are caused by the breakdown of this tolerance, and T cell activation leads to severe inflammation and tissue damage. For example, in rheumatoid arthritis, synovial joints will be destroyed whereas in insulin-dependent diabetes mellitus (IDDM, type 1 diabetes), insulin-producing beta cells in the pancreatic islets of Langerhans will be the focus of the attack. The genetic makeup of susceptible individuals and the environmental factors leading to autoimmunity are complex and largely unknown. In many instances, the main genetic locus ... Read more

Single nucleotide polymorphisms (SNPs) often represent allelic variants of genes. The differences between individuals within a species are mainly due to SNPs. SNPs are commonly used as genetic markers for genetic diseases and other phenotypic traits. Currently, throughput and accuracy are limiting factors in the widespread use of SNPs in diagnostics (Kwok, 2001). A large number of both individuals and SNPs often have to be screened when searching for correlation between specific alleles and phenotypic traits. SNP genotyping analysis of one sample at a time is extremely costly and time consuming. Pooling DNA samples prior to quantitative SNP allele frequency ... Read more