The University of Hong Kong

The Chinese University of Hong Kong

Versitech, Inc.

British Columbia Cancer Agency Branch

Lit Man Poon

Kwok Yung Yuen

Yi Guan

Kwok Hung Chan

John M Nicholls

Yuk Ming Dennis Lo

Joseph S M Peiris

Frederick C Leung

Joseph Sriyal Malik Peiris

Yuk Ming Lo

Chiu Yat Patrick Woo

Kar Pui Susanna Lau

Steven J Jones

Jianghong An

Allan Sik-Yin Lau

Hing Yee Law

Chun Wai Davy Lee

Lok Yan Fan

Presented herein are live-attenuated viruses and methods of generating thereof from a parental virus through a plurality of nucleotide substitutions in the viral genome. The nucleotide substitutions result in a change in codon usage bias within codons of one or more protein encoding sequences and no change in amino acid sequences of the proteins. The live-attenuated viruses display unaltered replication in avian hosts for propagation, but attenuated replication in mammalian hosts, when compared to the replication of the parental virus. The live-attenuated viruses in a form of improved vaccines can be used to elicit protective immune responses.

Live-attenuated virus and methods of production and use

In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

Methods for detecting DNA orginating from different individuals

The present invention provides pyrimidinyl compounds of formula (I) and pharmaceutically acceptable salts thereof. These compounds may be used for the inhibition of influenza. In particular, the compounds of the invention may be used for the treatment or prophylaxis of influenza A, most particularly H1N1 or H5N1 influenza. The compounds of the invention can also be used for the treatment or prophylaxis of a disease caused by, an orthomyxovirus, a paramyxovirus, a parainfluenza virus, mumps virus, Newcastle disease virus, fowl plague virus or Sendai virus. 

Anti-influenza compounds

Methods for detecting DNA originating from different individuals

The present invention relates to an isolated novel virus causing Severe Acute Respiratory Syndrome (SARS) in humans ('hSARS virus'). The hSARS virus is identified to be morphologically and phylogenetically similar to known member of Coronaviridae. The present invention provides the complete genomic sequence of the hSARS virus. Furthermore, the invention provides the nucleic acids and peptides encoded by and/or derived from the hSARS virus and their use in diagnostic methods and therapeutic methods, including vaccines. In addition, the invention provides chimeric or recombinant viruses encoded by said nucleotide sequences and antibodies immunospecific to the polypeptides encoded by the nucleotide sequences.

Human virus causing severe acute respiratory syndrome (SARS) and uses thereof

The present invention provides the complete genomic sequence of a novel human coronavirus, coined as coronavirus-HKU1 ('CoV-HKU1'), isolated in Hong Kong from a patient who had a recent history of visit to Schenzhen, China. The virus belongs to the order Nidovirales of the family Coronavirdae, being a single-stranded RNA virus of positive polarity. The invention also provides the deduced amino acid sequences of the complete genome of the CoV-HKU1. The nucleotide sequences and deduced amino acid sequences of the CoV-HKU1 are useful in preventing, diagnosing and/or treating the infection by CoV-HKU1. Furthermore, the invention provides immunogenic and vaccine preparations using recombinant and chimeric forms as well as subunits of the CoV-HKU1 based on the nucleotide sequences and deduced amino acid sequences of the CoV-HKU1.

Human virus causing respiratory tract infection and uses thereof

The present invention provides the complete genomic sequence of a novel human coronavirus, coined as coronavirus-HKU1 ('CoV-HKU1'), isolated in Hong Kong from a patient who had a recent history of visit to Schenzhen, China. The virus belongs to the order Nidovirales of the family Coronaviridae, being a single-stranded RNA virus of positive polarity. The invention also provides the deduced amino acid sequences of the complete genome of the CoV-HKU1. The nucleotide sequences and deduced amino acid sequences of the CoV-HKU1 are useful in preventing, diagnosing and/or treating the infection by CoV-HKU1. Furthermore, the invention provides immunogenic and vaccine preparations using recombinant and chimeric forms as well as subunits of the CoV-HKU1 based on the nucleotide sequences and deduced amino acid sequences of the CoV-HKU1.

The present invention relates to a high-throughput diagnostic assay for the virus causing Severe Acute Respiratory Syndrome (SARS) in humans ('hSARS virus'). In particular, the invention relates to a high-throughput reverse transcription-PCR diagnostic test for SARS associated(SARS-CoV). The present assay is a rapid, reliable assay which can be used for diagnosis and monitoring the spread of SARS and is based on the nucleotide sequences of the N (nucleocapsid)-gene of the hSARS virus. The present method eliminates false negative results and provides increased sensitivity for the assay. The invention also discloses the S (spike)-gene of the hSARS virus. The invention further relates to the deduced amino acid sequences of the N-gene and S-gene products of the hSARS virus and to the use of the N-gene and S-gene products in diagnostic methods. The invention further encompasses diagnostic assays and kits comprising antibodies generated against the N-gene or S-gene product.

High-throughput diagnostic assay for the human virus causing severe acute respiratory syndrome (SARS)

The present invention relates to a diagnostic assay for the virus causing Severe Acute Respiratory Syndrome (SARS) in humans ('hSARS virus'). In particular, the invention relates to a real-time quantitative PCR assay for the detection of hSARS virus using reverse transcription and polymerase chain reaction. Specifically, the quantitative assay is a TaqMan&#xae; assay using the primers and probes constructed based on the genome of the hSARS virus. The invention further relates to a diagnostic kit that comprises nucleic acid molecules for the detection of the hSARS virus.

Diagnostic assay for the human virus causing severe acute respiratory syndrome (SARS)

Embodiments of the present invention are directed to the detection of fetal or maternal RNA in a blood sample from a pregnant subject, and may involve subjecting the sample to a test for fetal or maternal analysis indicative of a fetal or maternal condition or characteristics. For instance, the RNA analysis may involve the assessment of the gene expression pattern of an unborn fetus by analyzing a blood sample from the mother. The prenatal monitoring technology allows, for the first time, the detection of genes which are expressed by the fetus, just by analysis of a sample of maternal blood. In specific embodiments, the prenatal monitoring technology is based on the discovery of circulating RNA of fetal origin in the plasma of pregnant women. In general, the detection method performed on a maternal serum or plasma sample from a pregnant female comprises detecting the presence of RNA of fetal or maternal original in the sample.

Growing community of inventors

Hong Kong, China

Lit Man Poon