Abstract: Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.

Abstract: Disclosed herein is a dynamically interactive combination of a shoe and an externally adjustable internal orthotic foot cradle formed of a fabric strap material. The disclosed combination attenuates and beneficially disperses the deforming forces experienced by the foot in weight bearing, limits the extent of pronation and excursions of the various joints of the mid and hind foot during weight bearing and the cradle can store mechanical energy absorbed during weight bearing and return at least a portion of such stored energy in the form of restorative forces applied to the mid and hind foot during the non-weight bearing phase of the gait cycle.