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This invention provides a novel family of acylthiols and uses thereof. More specifically, this invention provides effective inhibitors of HIV that selectively target its highly conserved nucleocapsid protein (NCp7) by interacting with metal chelating structures of a zinc finger-containing protein. Because of the mutationally intolerant nature of NCp7, drug resistance is much less likely to occur with compounds attacking this target.

Purines such as adenosine and ATP have been shown to play a wide array of roles in biological systems such as inter alia, modulator of vasodilation and hypotension, muscle relaxant, central depressant, inhibitor of platelet aggregation, regulator of energy supply/demand, responder to oxygen availability, neurotransmitter and neuromodulator. All P1 and P2 receptor nucleoside ligands suffer from chemical instability that is caused by the labile glycosidic linkage in the sugar moiety of the nucleoside.

To date there have been no adequate methods to determine the frequency of mutations in humans. This invention discloses a method of measuring the mutational frequency of a mitochondrial DNA sequence by sequencing mitochondrial DNA from clonally expanded single cells such as CD34+ human stem cells. Sequencing for mitochondrial DNA polymorphisms and mutations may also be useful as a general method to detect minimal residual disease in leukemia. The mitochondrial genome is particularly susceptible to mutations and these may be used to measure genomic mutagenesis by virtue of comparison.

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States. Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults. Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities. Improved diagnostics are needed for assessing the risks of developing this debilitating disease.

This invention portrays a simple method for treatment of antigen-deficiency diseases by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. This method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Tumor Necrosis Factor alpha (TNF-alpha) is a multifunctional cytokine that mediates inflammation, immune regulation, and cellular proliferation. This cytokine is converted to its active form by TNF-alpha converting enzyme (TACE). Pathological increases in TNF-alpha activity have been associated with a wide variety of inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer. Inhibiting the conversion of TNF-alpha to its active form by inhibiting TACE represents a potential treatment for these diseases.

Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

Expression of the HIV-1 Vif protein in the absence of other viral factors such a Tat and Rev is extremely inefficient due to the presence of inhibitory sequences on its mRNA. This invention uses codon optimization to remove such inhibitory sequences without altering the amino acid sequence of the protein. The modified vif gene in the resulting pcDNA -hVIF vector is expressed under the control of the CMV promoter. In this, the protein functions as wild type and is more amendable to high-level expression in mammalian cells.

Currently, adeno-associated virus (AAV) represents the gene therapy vehicle of choice because it has many advantages over current strategies for therapeutic gene insertion. AAV is less pathogenic than other virus types; stably integrates into dividing and non-dividing cells; integrates at a consistent site in the host genome; and shows good specificity towards various cell types for targeted gene delivery.