Robert Evans Rhoads

US Patent:

7074596, Jul 11, 2006

Filed:

May 17, 2002

Appl. No.:

10/150718

Inventors:

Edward Darzynkiewicz - Warsaw, PL
Robert E. Rhoads - Shreveport LA, US
Janusz Stepinski - Warsaw, PL

Assignee:

Board of Supervisors of Louisiana State University And Agricultural and Mechanical College - Shreveport LA

International Classification:

C12P 19/36
C12P 19/34
C12Q 1/68
C12Q 1/70
C07H 21/02

US Classification:

435 90, 435 5, 435 6, 435 91, 435 911, 435 9151, 536 231, 536 232, 536 254

Abstract:

The ability to synthesize capped RNA transcripts in vitro has been of considerable value in a variety of applications. However, one-third to one-half of the caps have, until now, been incorporated in the reverse orientation. Such reverse caps impair the translation of in vitro-synthesized mRNAs. Novel cap analogues, such as P-3′-deoxy-7-methylguanosine-5′P-guanosine-5′triphosphate and P-3′-O,7-dimethylguanosine-5′P-guanosine-5′triphosphate, have been designed that are incapable of being incorporated into RNA in the reverse orientation. Transcripts produced with SP6 polymerase using “anti-reverse” cap analogues were of the predicted length. Analysis of the transcripts indicated that reverse caps were not formed. The in vitro translational efficiency of transcripts with the novel “anti-reverse” cap analogues was significantly higher than that of transcripts formed with conventional caps.

US Patent:

8153773, Apr 10, 2012

Filed:

Jun 19, 2008

Appl. No.:

12/280282

Inventors:

Jacek Jemielity - Warsaw, PL
Joanna Kowalska - Radom, PL
Edward Darzynkiewicz - Izabelin, PL
Robert E. Rhoads - Shreveport LA, US

Assignee:

Board of Supervisors of Louisiana State University and Agricultural and Mechanical College - Baton Rouge LA
University of Warsaw - Warsaw

International Classification:

C07H 21/00
C12Q 1/68
C12P 19/34
A61K 38/00

US Classification:

536 231, 536 243, 435 61, 435 911, 435 912, 530300

Abstract:

New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2′-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are “anti-reverse cap analogs” (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog mGpppG.

US Patent:

8519110, Aug 27, 2013

Filed:

Jun 4, 2009

Appl. No.:

12/996243

Inventors:

Joanna Kowalska - Radom, PL
Jacek Jemielity - Warsaw, PL
Edward Darzynkiewicz - Warsaw, PL
Robert E. Rhoads - Shreveport LA, US
Maciej Lukaszewicz - Warsaw, PL
Joanna Zuberek - Warsaw, PL

Assignee:

Board of Supervisors of Louisiana State University And Agricultural and Mechanical College - Baton Rouge LA

International Classification:

C12Q 1/68
C12N 15/00
C07H 21/02
C07H 21/04

US Classification:

536 231, 536 241, 435 61, 435440

Abstract:

Dinucleotide cap analogs are disclosed, modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group. The analogs are useful as reagents in the preparation of capped mRNAs and have increased stability both in vitro and in vivo. They may be used as inhibitors of cap-dependent translation. Optionally, the boranophosphate or phosphoroselenoate group has a 2′-O or 3′-O-alkyl group, preferably a methyl group, producing analogs called BH-ARCAs or Se-ARCAs. ARCAs may be modified with α-, β-, or γ-boranophosphate or phosphoroselenoate groups.

US Patent:

20060252115, Nov 9, 2006

Filed:

Jul 10, 2006

Appl. No.:

11/483483

Inventors:

Edward Darzynkiewicz - Warsaw, PL
Robert Rhoads - Shreveport LA, US
Janusz Stepinski - Warsaw, PL

International Classification:

C12P 21/06
C07H 21/02
C07H 19/04

US Classification:

435068100, 435320100, 536023100, 536026100

Abstract:

The ability to synthesize capped RNA transcripts in vitro has been of considerable value in a variety of applications. However, one-third to one-half of the caps have, until now, been incorporated in the reverse orientation. Such reverse caps impair the translation of in vitro-synthesized mRNAs. Novel cap analogues, such as P-3′-deoxy-7-methylguanosine-5′ P-guanosine-5′ triphosphate and P-3′-O,7-dimethylguanosine-5′ P-guanosine-5′ triphosphate, have been designed that are incapable of being incorporated into RNA in the reverse orientation. Transcripts produced with SP6 polymerase using “anti-reverse” cap analogues were of the predicted length. Analysis of the transcripts indicated that reverse caps were not formed. The in vitro translational efficiency of transcripts with the novel “anti-reverse” cap analogues was significantly higher than that of transcripts formed with conventional caps.

US Patent:

47105666, Dec 1, 1987

Filed:

Dec 27, 1984

Appl. No.:

6/686708

Inventors:

John W. Kozarich - College Park MD
Robert E. Rhoads - Lexington KY

Assignee:

Yale University - New Haven CT

International Classification:

C07H 1906
C07H 1910
C07H 1916

US Classification:

536 28

Abstract:

The synthesis of a new affinity medium, the p-aminophenyl-. gamma. -ester of 7-methylguanosine-5'-triphosphate coupled to Sepharose, for use in affinity chromatography is claimed. An improved method in terms of speed and purity for the isolation of messenger ribonucleic acid cap-binding protein is claimed. The synthesis of the p-aminophenyl-. gamma. -ester of 7-methylguanosine-5'-triphosphate is described.

US Patent:

56460090, Jul 8, 1997

Filed:

Jan 19, 1994

Appl. No.:

8/184632

Inventors:

Robert E. Rhoads - Shreveport LA
Arrico De Benedetti - Shreveport LA

Assignee:

The University of Kentucky Research Foundation - Lexington KY

International Classification:

C12P 2106
C12N 500
C12N 1563

US Classification:

435 691

Abstract:

A hybrid vector carrying a first and second DNA segments operationally linked thereto, the first DNA segment encoding a protein capable of cross-linking to the cap structure of mRNA and mediating ribosome-binding, and the second DNA segment encoding a polypeptide or protein, the vector being capable of replication, transcription and translation to express the factor and the polypeptide or protein upon transformation of a eukaryotic host, and the polypeptide or protein being expressed at a level higher than the level of expression thereof in the absence of the first DNA segment. A eukaryotic host is transformed with this hybrid vector. Also disclosed is a method of increasing the synthesis of a polypeptide or protein in a eukaryotic host cell.

US Patent:

61803855, Jan 30, 2001

Filed:

Oct 25, 1996

Appl. No.:

8/736915

Inventors:

Timothy Skern - Hainburg/Donau, AT
Regina Kirchweger - Oed/Amstetten, AT
Elisabeth Ziegler - Vienna, AT
Dieter Blaas - Vienna, AT
Hans-Dieter Liebig - Vienna, AT
Barry J. Lamphear - Shreveport LA
Debra Waters - Lafayette LA
Robert E. Rhoads - Shreveport LA
Wolfgang Sommergruber - Purkersdorf, AT
Horst Ahorn - Weigelsdorf, AT

Assignee:

Boehringer Ingelheim Vetmedica GmbH - Ingelheim am Rhein

International Classification:

C12N 950
C07H 2104

US Classification:

435219

Abstract:

Methods of making and using Picornavirus L proteinase peptides (PLPPs) are provided, including, but not limited to, expression of DNA encoding all or a portion thereof, such as a Picornavirus L proteinase (PLP) and variants thereof, as well as methods for determining active sites and inhibitors of a PLP.