Columbia Technology Ventures

Nucleic acid sequences and antibodies for the diagnosis of Kaposi's Sarcoma-associated herpesvirus (KSHV/HHV8)

Lead Inventors: Yuan Chang, M.D.; Patrick Moore, M.D., M.P.H. Tech Ventures Reference: IR 425 Novel sequences from the viral genome of Kaposi's sarcoma-associated herpesvirus/ human herpesvirus 8 (KSHV/HHV8) allow diagnosis of virally induced cancers in Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is the major cause of Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma. These virally induced cancers, which are prevalent in immunocompromised populations including HIV/AIDS patients and the elderly, result in body cavity tumors. Because these cancers are the result of viruses, they are most effectively treated during the early stages of pathogenesis. This technology provides a tool to diagnose KSHV/HHV8 in human patients by elucidating unique nucleic acid sequences in the viral genome and providing antibodies to the proteins that they encode. Because this technology allows the diagnosis of KSHV/HHV8 in any tissues that are affected, it can be used directly on patients, on donor blood samples, or on donor organs for organ transplantation. As this technology uses genetic technology, amplification is possible from small samples, and sample collection can be non-invasive. This technology is the only known method to genetically identify KSHV/HHV8 infection and is useful in at-risk patient screening, blood and organ screening, and other diverse applications. For the first time, the diagnosis of KSHV/HHV8 will be possible with quick and reliable DNA-based tests coupled with antibody-based verification to allow for early detection and intervention. Various DNA-based genetic diagnostic tests have become common in both lab and clinical settings. The unique DNA sequences described here can be used in these same genetic diagnostic tests to detect KSHV/HHV8 at the earliest stages of infection. Moreover, antibodies generated against antigens produced from these DNA sequences are described and can be used as confirmation of a diagnosis or as first-line tests themselves. Because this technology relies primarily on genetic technology for the diagnosis of KSHV/HHV8, it provides a more sensitive, less expensive, and simpler way to diagnose infection. These sequences were originally isolated from patients who had been infected with KSHV. After isolation, cutting edge gene sequencing techniques were employed to find unique genetic markers arising from the KSHV rather than the patient's own cells. Because these sequences were originally isolated from human patients, it is probable that they will continue to be effective as a diagnostic tool on new patients. Moreover, these technologies have been tested against existing tissue libraries to demonstrate their efficacy. Applications: • The unique DNA sequences can be used in PCR or Southern blot based assays to diagnose KSHV/HHV8 in tumor samples, blood samples, organ samples, or any other tissue sample. • Beyond diagnosing patients who are suspected to have contracted KSHV/HHV8, these diagnostic tools could be used as a standard screen in blood or organ donations. • Antibodies generated from these unique DNA sequences can be used diagnostically to detect antigens in patient tissues or to detect an immunological response in patient blood. • These DNA sequences can be used to produce large quantities of antigen to help develop a vaccine against KSHV/HHV8 Advantages: • This technology is sensitive enough to diagnose KSHV/HHV8 in patients before they begin to show symptoms. For at-risk populations, these diagnostic tools could be invaluable. • This technology uses DNA sequences that are specific for KSHV/HHV8. This makes it a much more accurate diagnostic tool than histological samples. • Antibodies produced from these DNA samples are specific for KSHV/HHV8 reducing off target diagnostic or therapeutic action. Additionally, their specificity could lead to greater efficacy over generalized tumor treatments. • Using these DNA sequences and antibodies, therapeutics could be generated specifically for the underlying cause of KSHV/HHV8 rather than for the symptoms associated with the disease. Patent information -- see links below: 6,150,093 5,801,042 6,183,751 6,830,759 6,500,663 6,093,550 7,932,066 Licensing Status: Available for licensing and sponsored research support Related Publications: -- Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma, Science 1994 Dec 16;266(5192):1865-9. -- Russo JJ, Bohenzky RA, Chien MC, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore PS. Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8), Proc. Natl. Acad. Sci. U S A. 1996 Dec 10;93(25):14862-7.