Ranjit S Bindra15 Orange St, New Haven, CT 06510

2011026, Oct 27, 2011

Apr 21, 2011

13/091918

Jacob del Campo - North Haven CT, US
Erica Beth Schleifman - New Haven CT, US
Ranjit S. Bindra - New York NY, US
Peter M. Glazer - Guilford CT, US

A61K 35/12
A61P 31/18
A61K 31/7088
C12N 15/01
C12N 5/071

424 937, 435441, 435366, 514 44 R

Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that displace the polypyrimidine strand of target duplex and form a triple-stranded structure and hybrid duplex in a sequence specific manner with the polypurine strand of the target duplex. The triplex-forming molecules include a mixed-sequence “tail” which increases the stringency of binding to the target duplex, improves the frequency of modification at the target site, and reduces the requirement for a polypurine:polypyrimidine stretch. Methods for using the triplex-forming molecules in combination with one or more donor oligonucleotides for targeted modification of sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV) are also disclosed. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.

2011029, Dec 1, 2011

Apr 21, 2011

13/091921

Jacob del Campo - North Haven CT, US
Ranjit S. Bindra - New York NY, US
Peter M. Glazer - Guilford CT, US

A61K 48/00
A61P 3/00
C12Q 1/68
A61P 43/00
C07H 21/00
A61K 38/08

424 9321, 514 44 R, 536 231, 514 218, 435 618

Compositions and methods for treating lysosomal storage diseases are disclosed. Lysosomal dysfunction is usually the result of deficiency of a single enzyme necessary for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides which are fated for breakdown or recycling. The compositions contain triplex-forming molecules which can be used to induce site-specific homologous recombination in mammalian cells when combined with donor DNA molecules, by stimulating cellular DNA synthesis, recombination, and repair mechanisms. The methods are particular useful for correcting point mutations in genes associated with lysosomal storage diseases such as Gaucher's disease, Fabry disease, and Hurler syndrome. Methods for determining the frequency of target gene repair and assessing the restoration of the enzymatic activity of corrected polypeptides are also disclosed. Ex vivo and in vivo methods of gene correction in patients are also provided.

2010017, Jul 8, 2010

Jan 11, 2008

12/522804

Peter M. Glazer - Guilford CT, US
Ranjit Bindra - New York NY, US
Erica B. Schleifman - New Haven CT, US

A61K 35/12
C12N 15/87
A61K 38/16
C12N 5/00
A61P 31/18

424 937, 435463, 514 8, 435325

Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that bind to duplex DNA in a sequence specific manner at target sites to form triple-stranded structures. The triplex-forming molecules can be triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs). The triplex-forming molecules are useful to induce site-specific homologous recombination in mammalian cells when used in combination with donor oligonucleotides. The triplex-forming molecules target sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV). This binding stimulates homologous recombination of a donor oligonucleotide to cause mutations in HIV cell surface receptor genes that result in one or more deficiencies in the ability of the encoded receptor to bind to HIV and allow its transport into the cell. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.