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Background: Copolymers based on poly-[N-(2-hydroxypropyl) methacrylamide] (HPMA) have been used previously to enable targeted delivery of adenovirus. Here we demonstrate polymer-coating techniques can also be used to modify and retarget adeno-associated virus (AAV) types 5 and 8., Methods: Three strategies for modifying transductional targeting of AAV were employed. The first involved direct reaction of AAV5 or AAV8 with amino-reactive HPMA copolymer. The second approach used carbodiimide (EDC) chemistry to increase the number of surface amino groups on the AAV5 capsid, thereby improving coating efficiency. In the third approach, the AAV5 genome was isolated from capsid proteins and delivered in a synthetic polyplex consisting of polyethylenimine (PEI) and HPMA., Results: Efficient covalent attachment of HPMA copolymer to AAV5 could only be achieved following modification of the virus with EDC. Coating inhibited sialic acid dependent infection and provided a platform for retargeting via new ligands, including basic fibroblast growth factor. Retargeted infection was shown to be partially resistant to neutralising antisera. Delivery of AAV5 genomes using PEI and HPMA was efficient and provided absolute control of tropism and protection from antisera. In contrast AAV8 could be reacted directly with HPMA copolymer and allowed specific retargeting via the epidermal growth factor receptor, but gave no protection against neutralising antisera., Conclusions: Reactive HPMA polymers can be used to ablate the natural tropism of both AAV8 and EDC-modified AAV5 and enable receptor-specific infection by incorporation of targeting ligands. These data show transductional targeting strategies can be used to improve the versatility of AAV vectors., ((c) 2008 John Wiley & Sons, Ltd.)

Background: With declining U.S. medical student interest in family medicine, it is important to study factors that may predict for individual residency program fill rates. Predictors of family medicine residency program match rates are few, with location by region of the country being the best predictor. Using a limited database, this study evaluated whether community-based residency program match rates are associated with patient visit volume and payer status., Methods: An existing database of characteristics of 42 community-based family medicine residency programs was analyzed for associations of match rate with patient visit volume and with insurance payer status., Results: Nonsignificant correlations were calculated for match rate with the following factors: patient visit volume per provider, percentage of patient visits with no insurance or with Medicaid payment, percentage of visits with Medicare payment, and percentage of visits with private third party payers. A marginal negative association of match rate with percentage of patient visits with Medicare payment was not significant when adjusted for region of the country., Conclusions: In this study, neither patient visit volume nor payer status were predictive of match rate for community-based family medicine residency programs. Limitations to this study are acknowledged.

This review focuses on the growing field of research concerned with the application of adenovirus proteins to improve the transfection efficiency of synthetic gene delivery systems. Several adenovirus component proteins influence cellular activity of the infecting adenovirus and the overall effect is a highly regulated and efficient infection pathway. It is possible that some of these proteins may be incorporated into synthetic gene delivery vectors, to Improve specific components of their cellular processing and improve transfection activity. Several adenovirus proteins have been introduced into synthetic vector systems. In particular, the penton base, which participates in cellular entry and endosomal escape of the adenovirus, shows an ability to increase cellular uptake and cytoplasmic penetration of synthetic systems. Similarly, hexon, the major adenovirus coat protein, is involved in the nuclear delivery of the infecting virus and can be exploited for enhancing nuclear targeting of synthetic systems. The possibility of using classical nuclear localization sequences from adenovirus proteins has also been evaluated. Finally, there is considerable interest in the use of adenovirus core proteins, such as mu, to improve properties of DNA condensation and unpackaging following the arrival of synthetic vectors in the nuclei of target cells.