This project is a collaborative effort between Viagene Inc. and the University of Virginia. A recently discovered cis-acting element from Mason-Pfizer Monkey Virus (MPMV) will be utilized for the development of novel retroviral vectors expressing (Human Immunodeficiency Virus) HIV gene products. The MPMV element can efficiently substitute for the HIV rev protein and the Rev Response Element (RRE) in the transport of HIV gag/pol and env mRNAs from the nucleus to the cytoplasm and has been named CTE (constitutive transport element). This element can also substitute for rev in HIV replication. The CTE will be exploited for the development of retroviral vectors expressing HIV gag/pol and env proteins in a rev independent manner. These will include classical Moloney based vectors as well as vectors based on Simian Immunodeficiency Virus (SIV). In addition, we propose to use the CTE to construct SIV vectors for the delivery of transdominant negative rev genes. Pilot studies will also be performed to determine if the element can function to facilitate the expression of cDNAs from intron-containing cellular genes that are normally difficult to express. The vectors that will be made in this program could be commercially developed for use in HIV vaccination, therapy and diagnostics.
