On p. 165, Redfern et al. report the creation of transgenic mice that inducibly express a Gi–coupled k opioid receptor altered so as to be nonreponsive to its natural ligand, but responsive to the small–molecule spiradoline. Using the tetracycline transactivator system, they induced expression of this engineered receptor (Ro1) in the heart, liver, and salivary gland of transgenic mice. Activation of Ro1 by spiradoline in the heart resulted in a 50% decrease in heart rate in less than 1 min. As G–protein receptors are pivotal in numerous intracellular signaling pathways, this system could prove useful for dissecting their role in complex physiological processes (see also p. 131 ).

AAV vectors are promising candidates for human gene therapy. The inability of AAV to bind cells lacking the heparan sulfate proteoglycan, however, has limited the range of cells that can be targeted. Using a bispecific antibody that recognizes the platelet–specific αIIbβ3 integrin and the AAV capsid structure, Bartlett et al. have successfully transduced megakaryocyte cell lines recalcitrant to infection by wild–type AAV (p. 181). Interestingly, the bispecific antibody also appeared to reduce the endogenous tropism of the AAV vector for heparan sulfate bearing cells.