Boston University

Other

University of California

US Government As Represented by the Secretary of the Army

Sequenom, Inc.

Univ. of Mass. Medical Center

Cassandra L Smith

Charles Cantor

Takeshi Sano

Przemyslaw Szafranski

David L Kaplan

Charlene M Mello

Christof M Niemeyer

Kenneth A Marx

Mary Rusckowski

Donald J Hnatowich

Dong-Jing Fu

Sandor Vajda

Gabriel O Reznik

Marek Przetakiewicz

Hubert K&ouml;ster

Hubert Köster

Takashi Ito

Mark W Pandori

Ron Yaar

Marek Prezetakiewiczr

The back scrubber is a hygienic device. The back scrubber is adapted for use with a person. The back scrubber is configured for use in bathing. The back scrubber is configured for use with soap. The back scrubber extends the reach of the person such that soap may be applied to otherwise inaccessible locations of the person. The back scrubber comprises a head, a handle, and a control system. The control system is installed in the handle. The head attaches to the handle. The head contains the soap. The handle extends the reach of the person. The control system adjusts the overall length of the handle.

Back scrubber

The invention relates to supramolecular bioconjugates and to methods for assembling and utilizing supramolecular bioconjugates. Supramolecular bioconjugates comprise a plurality of first nucleic acids and a plurality of mediators wherein each mediator comprises a second nucleic acid complementary to a sequence within said plurality of first nucleic acids. To assemble a supramolecular bioconjugate, one or more sets of bioreactive agents are coupled to the plurality of mediators, forming a plurality of bioreactive complexes The plurality of bioreactive complexes are hybridized to the plurality of first nucleic acids to form the supramolecular bioconjugate. Bioconjugates can be used to detect and isolate targets, to screen samples for targets such as antigens, to treat patients with multiple agents or to diagnose disorders in the form of a kit.

Nucleic acid directed immobilization arrays and methods of assembly

This invention is directed to methods and reagents useful for sequencing nucleic acid targets utilizing sequencing by hybridization technology comprising probes, arrays of probes and methods whereby sequence information is obtained rapidly and efficiently in discrete packages. That information can be used for the detection, identification, purification and complete or partial sequencing of a particular target nucleic acid. When coupled with a ligation step, these methods can be performed under a single set of hybridization conditions. The invention also relates to the replication of probe arrays and methods for making and replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3&#x2032;-overhangs.

Arrays of probes for positional sequencing by hybridization

Methods for detecting and sequencing of target double-stranded nucleic acid molecules, nucleic acid probes and arrays of probes useful in these methods, and kits and systems that contain these probes are provided. The methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes include a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments.

Solid phase sequencing of double-stranded nucleic acids

This invention relates to methods for detecting and sequencing of target double-stranded nucleic acid sequences, to nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probe comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include nucleic acids in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated determination of molecular weights and identification of the target sequence.

Compounds and methods are described for producing streptavidin mutants with changed affinities. In particular, modifications to the sequence of the natural streptavidin gene is described to create amino acid substitutions resulting in greater affinity for biotin substitutes than for biotin.

Multiflavor streptavidin

Compositions and methods for the control of genetically engineered organisms are described. A more effective cell suicide approach is contemplated based on the conditional expression of the lethal,streptavidin gene. Toxicity of streptavidin is derived from its exceptionally high binding affinity for an essential prosthetic group, D-biotin. The general requirement for biotin through the living world makes streptavidin-based conditional lethal designs applicable to a broad range of containment strategies.

Compositions and methods for controlling genetically engineered organisms

The present invention relates to streptavidin proteins and peptides having a altered physical properties such as an increased stability or increased or decreased affinity for binding biotin. The invention also relates to methods for the detection, identification, separation and isolation of targets using streptavidin proteins or peptides. Streptavidin with increased or reduced affinity allows for the use of the streptavidin-biotin coupling systems for detection and isolation systems wherein it is necessary to remove of one or the other of the binding partners. Such systems are useful for the purification of functional proteins and viable cells. The invention also relates to nucleic acids which encode these streptavidin proteins and peptides and to recombinant cells such as bacteria, yeast and mammalian cells which contain these nucleic acids.

Streptavidin mutants

This invention is directed to methods and reagents useful for sequencing nucleic acid targets utilizing sequencing by hybridization technology comprising probes, arrays of probes and methods whereby sequence information is obtained rapidly and efficiently in discrete packages. That information can be used for the detection, identification, purification and complete or partial sequencing of a particular target nucleic acid. When coupled with a ligation step, these methods can be performed under a single set of hybridization conditions. The invention also relates to the replication of probe arrays and methods for making and replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.

Positional sequencing by hybridization

The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Self-assembling multimeric nucleic acid constructs

The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.

Method for replicating an array of nucleic acid probes

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.

Nucleic acid detection methods

The present invention relates to genetic containment systems which express a biotin-binding component that can be used for selectively destroying recombinant cells such as genetically engineered microorganisms. These systems may comprise a streptavidin or an avidin gene whose expression is controlled by a regulatable promoter. The regulatory agent such as a transcriptional effector is expressed from another gene which may also be expressed and its expression controlled by the containment system. Expression of the agent can be designed to respond to physiological changes in the environment. The invention also relates to containment systems and methods for the selective detection or tracking of recombinant cells and to eukaryotic and prokaryotic cells which contain these genetic containment systems.

Biotin-binding containment systems

A novel system and method for sensitive antigen detection. The system utilizes immuno-polymerase chain reaction in which a specific biotinylated nucleic acid molecule is used as the marker. The biotinylated marker is attached to antigen-antibody complex through a streptavidin-protein A chimeric protein that possesses tight and specific binding affinity both for biotin and immunoglobulin G. A segment of the attached biotinylated marker is amplified by polymerase chain reactions with appropriate primers and the polymerase chain reaction products are detected by agarose gel electrophoresis. The method can detect any antigen and has a greater sensitivity than any existing antigen detection system.

Growing community of inventors

Boston, MA, United States of America

Cassandra L Smith