Mutant activated gsalpha* and adenylyl cyclase 2 for use as therapeutic agents

摘要

The present invention relates to therapeutic uses of mutant activated Gs alpha and adenylyl cyclase 2. Although mutant activated Gs alpha has been, previously, associated with proliferative and physiological disorders of a subset of differentiated cells, it has now been discovered that mutant activated Gs alpha (referred to, hereafter, as Gs alpha *) can suppress proliferation as well as the transformed phenotype. Accordingly, in various embodiments of the present invention, introduction of Gs alpha * into cells or tissues, preferably by the use of viral vectors, may be used to reduce proliferation and/or prevent the development, reduce, or reverse malignancy. In further embodiments of the present invention, the introduction of adenylyl cyclase 2, preferably using viral vectors, may be used to limit cell proliferation and/or reduce the transformed phenotype. Because adenylyl cyclase 2 is not endogenous to most tissues but can be activated in a subset of malignant or otherwise proliferative cells (e.g., those in which growth factors stimulate phospholipases C and/or D), the introduction of adenylyl cyclase 2 may be used to selectively increase cAMP levels and thereby prevent, reduce, or reverse proliferation and/or malignancy and thus relieve the pathophysiological state.