Generally a gene knockdown agent should achieve high sequence
specificity and should lack off-target effects (non-antisense
effects due to interactions with structures other than gene
transcripts). Three major gene knockdown types are compared with
respect to offtarget effects and sequence specificities: 1)
phosphorothioate-linked DNA (S-DNA); 2) short interfering RNA
(siRNA); and, 3) Morpholino. S-DNAs cause multiple off-target
effects, largely because their backbone sulfurs bind to many
different proteins. S-DNAs also achieve poor sequence
specificity because S-DNA/RNA duplexes as short as 7 base-pairs
are cleaved by RNase H. siRNAs cause several off-target effects,
but improved designs may soon avoid such effects. siRNAs also
provide only limited sequence specificity because their short
guide sequences largely determine which gene transcripts will be
blocked or cleaved, and those guide sequences appear to
recognize insufficient sequence information to uniquely target a
selected gene transcript. This specif