Synthesis of Oligonucleotides 165
by an amino group to give a phosphorodiamidate morpholino (PMO) linkage (Figure 4.26). This type of mod-
ification has a number of advantages that have warranted its use in steric block antisense applications.^42
Such morpholino modifications give oligonucleotide analogues that are electrically neutral, show enhanced
binding to DNA and RNA, are completely nuclease resistant, and have lower toxicity and greater specificity
than phosphorothioate modifications. They have been used successfully in gene knockdown experiments
by microinjection into cells and embryos.
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