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Methods of enhancing engraftment of donor hematopoietic stem cells (HSCs) by reducing expression or activity of CXCR4 in HSCs is described. HSC are the only cells in the bone marrow that are both pluripotent and long lived. Bone marrow transplantation (BMT) using HSC is an increasingly common medical therapy for severe hematologic cancers and primary hematologic immunodeficiencies. However, for significant HSC engraftment to occur there must usually be pre-transplant conditioning with either irradiation or chemotherapy or both.

Available for licensing are methods to generate T cells responsive to multiple polyomaviruses. The resulting T cell populations could be useful in treating immunosuppressed individuals with polyomavirus infections or polyomavirus-associated pathologies such as Merkel cell carcinoma (MCC), polyomavirus-associated nephropathy (PVAN), hemorrhagic cystitis, progressive multifocal leukoencephalopathy (PML), and trichodysplasia spinulosa (TS). The methods could also be used to restore polyomavirus-specific immunity in immunocompromised individuals.

Investigators at the National Heart, Lung, and Blood Institute have designed a novel lentiviral vector as a potential gene therapy for sickle cell anemia and beta-thalassemia. The novel lentiviral vector encodes the beta-globin gene in a forward orientation and can produce 5-10 fold higher viral titer and 4-10 fold higher gene transfer efficiency to hematopoietic stem cells than reverse-oriented lentiviral vectors. In vivo studies conducted in rhesus macaques show beta-globin production after transplantation with this novel lentiviral vector.

Upon intranasal vaccination, live attenuated influenza vaccine (LAIV) viruses may replicate within the nose for several days. Current clinical diagnostic tests cannot distinguish between LAIV viruses and multiple influenza viruses in recently inoculated patients that present with respiratory symptoms. This poses a problem for the diagnosis and treatment of patients with respiratory symptoms, as these symptoms may not be caused by influenza. CDC researchers have developed a real-time RT-PCR assay to detect the presence of LAIV viruses.

Scientists at the NIH disclosed a mutated adeno-associated virus (AAV) serotype 5 by modifying sialic acid binding regions which mediate viral entry into host cells. Preliminary results from animal studies suggest that this modification can increase transduction by 3-4 folds in salivary glands and muscles, and can significantly decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV. Thus, the modified AAV5 vectors seem to be optimal for gene therapy.

Scientists at the NIH disclosed a novel adeno-associated virus (AAV) termed "44-9." AAV44-9 based vectors have high gene transfer activity in a number of cell types, including salivary gland cells, liver cells, and different types of neurons (e.g., cells of the cortex, olfactory bulb, and brain stem, and Purkinje cells of the cerebellum). These vectors can increase the transduction efficiency and decrease the potential of being neutralized by preexisting antibodies compared to the wild type AAV.

Knockout mouse is a valuable model to study biological functions of target genes. When Cre expressing mice are bred with mice containing a loxP-flanked gene, the gene between the loxP sites will be deleted in the offsprings. Scientists at the NIH have generated mNF-H-cre transgenic mouse lines that express Cre recombinase under the control of the promoter of the neurofilament-H gene, which is expressed in the late stage of neuronal maturation. The transgenic mice express cre in neurons (but not astrocytes) with highest expression in the cortex and hippocampus.

Herpes simplex viral infections, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), are exceptionally common worldwide. These viruses establish lifelong persistent infections with cycles of lytic reactivation to produce recurrent diseases including oral and genital lesions, herpetic keratitis/blindness, congenital-developmental syndromes, and viral encephalitis. Infection with HSV-2 increases the rate of human immunodeficiency virus (HIV) transmission in coinfected individuals. DNA replication inhibitors are typically used to treat herpesvirus infections.

Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified.