The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Fred Hutchinson Cancer Center

Stephen H Hughes

Yves Pommier

Terrence R Burke, Jr

Christophe Marchand

Xue Zhi Zhao

Steven Smith

Paul L Boyer

Mathieu Metifiot

Barry Johnson

Eugene Barsov

John A Brumbaugh

Victor E Marquez

Bao-Han C Vu

Andrea L Ferris

Vernon Pursel

Maqbool A Siddiqui

Pramod Sutrave

Ramesh Kumar

Maxine Linial

Carolyn Stenbak

Patrick Clark

A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH;Y is H or OH;each of Z-Zis independently H or halogen;Ris H, OH, NH, NHR, NRRor R;R, R, and Ris each independently H, halogen, OR, R, NHR, NRR, COR, CONRR, SONRR, or Rand Rtogether with the carbon atoms to which Rand Rare attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; andRand Ris each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or Rand Rtogether with the nitrogen to which Rand Rare attached form an optionally-substituted heterocycle.

Compounds for inhibiting drug-resistant strains of HIV-1 integrase

The invention provides for novel 2-Deoxyadenosine compounds, which can treat HIV infection at low cytotoxicity values. Substitution at the 4'-position provided compounds which demonstrated low cytotoxicity values in an ATP-based cytotoxicity assay.

C4'-substituted-2-deoxyadenosine analogs and methods of treating HIV

The present invention relates to a highly processive reverse transcriptase having DNA polymerase activity and substantially reduced protease activity. More specifically, the invention relates to an isolated reverse transcriptase from foamy virus comprising a substantially inactivated protease. The invention also relates to vectors containing the gene and hosts transformed with the vector of the invention. Further, the invention relates to a method for producing reverse transcriptase having DNA polymerase activity and substantially reduced protease activity by expressing the reverse transcriptase genes of the present invention in a recombinant host. Methods are also provided for producing cDNA from polynucleotides using the highly processive reverse transcriptase of the invention. Kits for the preparation of cDNA from RNA comprising the highly processive reverse transcriptase of the invention are also provided.

Foamy virus mutant reverse transcriptase

Recombinant avian sarcoma leukosis virus (ASLV)-derived retrovirus vectors having an expanded host range are described. The host range is expanded by the replacement of the ASLV envelope gene by an envelope gene from a virus capable of infecting both mammalian and avian cells. The resulting recombinant ASLV-derived retroviral vectors can replicate efficiently in avian cells, infect both avian and mammalian cells in high titer, and are replication-defective in mammalian cells. Thus, they are quite safe and advantageous for use in gene therapy and vaccines.

Retrovirus vectors derived from avian sarcoma leukosis viruses permitting transfer of genes into mammalian cells and therapeutic uses thereof

An Avian-derived retroviral vector from which the Constitutive Transport Element (CTE) has been removed and replaced with a genetic fragment from a mammalian virus in order to produce a vector that is replication competent in at least one non-native cell type without the need for a &ldquo;helper&rdquo; virus, and that is unlikely to recombine with endogenous mammalian viruses, making it both safe and simple to use in research and gene-therapy applications.

Use of constitutive transport elements for host range control

The present invention relates to DNA segments encoding chicken c-ski protein, to DNA constructs comprising the DNA segments and to cells transformed therewith. The present invention further relates to non-human transgenic mammals having increased muscle size and/or reduced fat. In addition, the present invention relates to methods of stimulating muscle growth and preventing degeneration of muscle, and to methods of treating muscle degenerative diseases and obesity.

Enhancement of musculature in non-human mammals expressing c-ski

The present invention relates to a method of detecting a DNA sequence by means of a DNA:DNA hybrid in real time using fluorescence. The present invention eliminates the need to use radioactive probes to detect the DNA and eliminates the delay needed for autoradiographic exposure of the X-ray to the radioactive label.

Method for the fluorescent detection of a DNA sequence in real time

Retrovirus vectors derived from avian sarcoma leukosis viruses

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Smithsburg, MD, United States of America

Stephen H Hughes