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To examine the effects of a ribozyme in VIVO, a major obstacle to overcome is the delivery of these molecules into the cells. A serious drawback of exogenous delivery is that the inhibitory effects of the nucleic acids so delivered are transient and require repeated administrations. Despite this, exogenously delivered molecules can incorporate chemical modifications, which Increase stability, although these modified bases and sugar-phosphate backbones can contribute to toxicity of the molecules. Further investigation is needed to establish whether the advantages of chemical modifications will overcome the general disadvantages of exogenous delivery.