Abstract: Morpholinos are widely used to block the activity of selected single-stranded genetic sequences. This invention comprises Morpholinos containing one or more integral photolinkers (Photo-Morpholinos) wherein the photolinkers are directly incorporated into the sequence of a Morpholino, where the photolinker has a size and structure which emulates the size and structure of a Morpholino subunit. This integrated photolinker design substantially simplifies and reduces cost of production relative to earlier photocleavable compositions. The invention also comprises use of these Photo-Morpholinos for modulating the expression of any selected gene transcript at any selected time and at any selected site simply by exposure to light. These Photo-Morpholinos afford a new use wherein a gene transcript is rendered inactive by contacting with a Photo-Morpholino—and then later exposure to light cleaves the Photo-Morpholino to inactive fragments—thereby reactivating that previously inactivated gene transcript.

Abstract: A method and comjugate for treating H. pylori infection in a subject are disclosed. The conjugate is composed of (a) a nuclease-resistant antisense oligomer effective to inhibit H. pylori infection in the subject by base-specific Watson-Crick binding to an H. pylori mRNA transcript, and (b) a transport moiety conjugated to the oligomer. The transport moiety is effective to facilitate uptake of the conjugate from the environment of the stomach into the cytoplasm of H. pylori cells by active transport or by pH-gradient transport across of the cell membrane of H. pylori. The conjugate is administered by oral route, preferably in a swellable polymer bolus designed to release the conjugate in sustained release.

Abstract: The invention relates to compositions and methods for rapidly detecting or isolating a target nucleic acid sequence in a polynucleotide-containing sample. The sample is exposed to a rapid pairing reagent, which contains a rapid capture component, effective to rapidly and non-selectively bind polynucleotides, and a target specific probe, effective to selectively bind the target nucleic acid sequence. Selectively disrupting the binding between the capture component and polynucleotides leaves only target sequence bound to the rapid pairing reagent.

Abstract: Polymeric compositions effective for delivering compounds in living organisms are described. The compositions include polypeptides which exhibit solubility in both hydrophilic and lipophilic environments by undergoing a reversible pH-dependent transition from a low-pH, lipophilic form to a high-pH, hydrophilic form.

Abstract: A method of generating a compound capable of interacting specifically with a selected macromolecular ligand is disclosed. The method involves contacting the ligand with a combinatorial library of oligomers composed of morpholino subunits with a variety of nucleobase and non-nucleobase side chains. Oligomer molecules that bind specifically to the receptor are isolated and their sequence of base moieties is determined. Also disclosed is a combinatorial library of oligomers useful in the method and novel morpholino-subunit polymer compositions.

Abstract: The present invention describes an assay system wherein target polynucleotide molecules are captured on a support by base-specific binding to support-bound polymers, which are themselves substantially uncharged, and the target polynucleotides can be detected on the basis of their backbone charge. The assay system may also include polycationic reporter molecules which are designed to bind to the fully charged analyte backbone, but not the uncharged (or substantially uncharged) polymer backbone. In one embodiment, the reporter molecules are composed of a polycationic moiety or tail designed to bind electrostatically to a fully charged polynucleotide, under conditions where the reporter does not bind to the less charged or uncharged binding polymer carried on the diagnostic reagent.

Abstract: A method of generating a compound capable of interacting specifically with a selected macromolecular ligand is disclosed. The method involves contacting the ligand with a combinatorial library of oligomers composed of morpholino subunits with a variety of nucleobase and non-nucleobase side chains. Oligomer molecules that bind specifically to the receptor are isolated and their sequence of base moieties is determined. Also disclosed is a combinatorial library of oligomers useful in the method and novel morpholino-subunit polymer compositions.

Abstract: The present invention describes a polymer composition effective to bind, in a sequence-specific manner to a target sequence of a duplex polynucleotide, at least two different-oriented Watson/Crick base-pairs at selected positions in the target sequence. The composition includes an uncharged backbone with 5- or 6-membered cyclic backbone structures and selected bases attached to the backbone structures effective to hydrogen bond specifically with different oriented base-pairs in the target sequence. Also disclosed are subunits useful for the construction of the polymer composition. The present invention further includes methods for (i) coupling a first free or polymer-terminal subunit, and (ii) isolating, from a liquid sample, a target duplex nucleic acid fragment having a selected sequence of base-pairs.

Abstract: Alpha-morpholino subunits and polymer compositions composed of alpha-morpholino subunits are disclosed. These subunits can be linked together by uncharged linkages, one to three atoms in length, joining the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide. The polymers of the instant invention can be used in place of standard RNA or DNA oligomers. For example, the target-specific polymers of the invention can be used in a variety of diagnostic assays for detection of RNA or DNA having a given target sequence. Further, the polymers of the invention also have potential use as therapeutic agents.

Abstract: Alpha-morpholino subunits and polymer compositions composed of alpha-morpholino subunits are disclosed. These subunits can be linked together by uncharged linkages, one to three atoms in length, joining the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide. The polymers of the present invention can be used in place of standard RNA or DNA oligomers for a number of standard laboratory procedures, for example, as probes in solid-phase systems and nucleic acid hybridization analyses. Further, the polymers of the present invention have potential use as therapeutic agents in anti-sense-type technologies.

Abstract: A polymer composition is disclosed composed of morpholino subunit structures linked together by uncharged, chiral linkages, one-three atoms in length. These chiral linkages join the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide.

Abstract: A polymer composition effective to bind in a sequence-specific manner to a target sequence of a duplex polynucleotide containing different Watson-Crick basepair oreientaions. The composition includes an uncharged backbone with 5- or 6-membered cyclic backbone structures and selected bases attached to the backbone structures effective to hydrogen bond specifically with different oriented basepairs in the target sequence.

Abstract: A polymer composition is disclosed composed of morpholino subunit structures which are linked together by uncharged, achiral linkages. These linkages are one to three atoms in length, joining the morpholino nitrogen of one subunit to the 5' exocyclic carbon of an adjacent subunit. Each subunit contains a purine or pyrimidine base-pairing moiety effective to bind by hydrogen bonding to a specific base or base-pair in a target polynucleotide.

Abstract: The crosslinking agent contains an acylhydrazide moiety, through which it is linked to a cytosine residue on the first chain; and an .alpha.-haloketal moiety which, after attachment of the crosslinking agent to the first chain, is hydrolyzed to an .alpha.-haloketone moiety, through which linking is effected to the base-paired guanine residue on the second chain.