摘要:
Cette invention concerne des procédés permettant de modifier des sites ciblés du génome, dans lequels on peut introduire dans le site ciblé des modifications recherchées qui peuvent être légères ou subtiles afin de modifier les gènes ciblés ou les séquences de régulation. On a découvert qu'on peut garder un marqueur sans que cela interfère avec le fonctionnement d'un gène ciblé ou qu'on peut le sélectionner pour effectuer l'excision d'ADN exogène afin de laisser une copie unique du gène ciblé comprenant la modification.
摘要:
On emploie la recombinaison homologue afin d'inactiver des gènes, notamment des gènes associés à des antigènes de complexes d'hystocompatibilité majeure (CHM). On a notamment inactivé le gène de beta2-microglobuline afin de réduire ou d'éliminer les antigènes de CHM de la classe A. On peut utiliser les cellules ainsi obtenues en tant que donneuses universelles. De plus, on peut modifier des cellules souche embryonnaires par recombinaison homologue, afin de les utiliser dans la production d'hôtes mammifères chimériques ou transgéniques.
摘要:
Single AAV vector constructs for regulated expression of an immunoglobulin molecule or fragment thereof and methods of making and using the same are described. The AAV vectors comprise a regulated promoter operably linked to the coding sequence for a first and second immunoglobulin coding sequence, a sequence encoding a self-processing cleavage site between the coding sequence for the first and second immunoglobulin coding sequence and a additional proteolytic cleavage site, which provides a means to remove the self processing peptide sequenc from an expressed immunoglobulin molecule or fragment thereof. The vector constructs find utility in enhanced production of biologically active immunoglobulins or fragments thereof in vitro and in vivo.
摘要:
Genetically modified cytokine-expressing cells for use as vaccines in the treatment of prostate cancer are provided. More specifically, genetically modified, GM-CSF expressing cells as a means to generate an enhanced immune response to beta filamin and the use thereof in the treatment of prostate cancer are described.
摘要:
Non-naturally occurring adenoviral vectors comprise a polynucleotide encoding an adenovirus death protein (ADP) polypeptide. The polynucleotide encoding ADP may be under transcriptional control of a cell-specific transcriptional regulatory element such as an α-fetoprotein transcriptional regulatory element.
摘要:
Compositions, methods and a system for external regulation of oncolytic virus replication are provided. The oncolytic virus contains a cell type-specific transcriptional regulatory element (CT-TRE) and an inducible transactivator regulated transcriptional regulatory element. The virus preferentially replicates in cells that allow a CT-TRE to function. In addition, the concentration of an inducing agent or condition is used to regulate a transactivator regulated transcriptional regulatory element, thereby providing at least two levels of control of oncolytic viral replication.
摘要:
The present invention relates to methods and compositions for increasing the production of high titer stocks or recombinant AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins. The methods and compositions of the invention are based on the observation that the low level expression of the AAV REP 78/68 protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titer recombinant viral stocks. The invention encompasses recombinant AAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of novel stable cell lines capable of generating high titer rAAV vectors. The invention provides methods for regulating the expression of the AAV REP 78/68, REP 40/52 and CAP gene at the transcriptional and post-transcriptional level.
摘要:
Therapeutic viral formulations having enhanced storage stability are described. The formulations comprise a viral vector in addition to one or more of an aqueous cosolvent, a reversible viral-encoded protease inhibitor and a mild reducing agent or other agent that prevents specific degradation of viral components.