Spadafora's laboratory originally discovered that mature sperm cells from a variety of species share the spontaneous ability to take up exogenous DNA molecules and deliver them to oocytes at fertilization: they called that phenomenon cell-mediated sperm-mediated gene transfer (SMGT). That feature was subsequently exploited, in their and other laboratories, to generate genetically modified animals in different species). They also found that sperm cells can also take up exogenous RNA molecules and transmit RNA-encoded genetic information in a process called reverse sperm-mediated gene transfer (SMRGT).
In further efforts to characterize the basic biological and molecular features underlying SMGT, they have identified a complex network of factors that are normally silent in spermatozoa, yet are activated soon after fertilization and contribute to early development. Among those, they have identified an endogenous reverse transcriptase RT activity (5, 6), they we have shown to play a central role in RSMGT and to be involved in the genesis and propagation of new genetic traits, besides those encoded by chromosomal genes and inheritable in a non-mendelian fashion.
"Our recent studies indicate that the relevant RT activity in this mode of genetic transmission originates from LINE-1 transposable elements and that it is indispensable in early murine embryonic development" says Spadafora.
In developments of these studies we found that the RT activity also plays key roles in cell transformation and cancer progression: indeed, both RT inhibition, and LINE-1 silencing, consistently inhibit cancer cell proliferation and promote their differentiation. These findings have formed the basis for the design of clinical trials using RT inhibitors in a novel differentiating cancer therapy (ongoing trials). Our current efforts are focussing on in-depth studies of RT-mediated molecular mechanisms implicated in normal development and in tumorigenesis.
