Fusion of Large Polypeptides to Human Adenovirus Type 5 Capsid Protein IX Can Compromise Virion Stability and DNA Packaging Capacity.

The human adenovirus (HAdV) protein IX (pIX) is a minor component of the capsid that acts in part to stabilize the hexon-hexon interactions within the mature capsid. Virions lacking pIX have a reduced DNA packaging capacity and exhibit thermal instability. More recently, pIX has been developed as a platform for presentation of large polypeptides, such as fluorescent proteins or large targeting ligands, on the viral capsid.

Human adenoviral DNA association with nucleosomes containing histone variant H3.3 during the early phase of infection is not dependent on viral transcription or replication.

Adenovirus (Ad) DNA undergoes dynamic changes in protein association as the virus progresses through its replicative cycle. Within the virion, the Ad DNA associates primarily with the virus-encoded, protamine-like protein VII. During the early phase of infection (∼6 h), the viral DNA showed declining association with VII, suggesting that VII was removed from at least some regions of the viral DNA.

Adenovirus-Mediated Expression of the p14 Fusion-Associated Small Transmembrane Protein Promotes Cancer Cell Fusion and Apoptosis In Vitro but Does Not Provide Therapeutic Efficacy in a Xenograft Mouse Model of Cancer.

Adenoviruses (Ads) are used in numerous preclinical and clinical studies for delivery of anti-cancer therapeutic genes. Unfortunately, Ad has a poor ability to distribute throughout a tumor mass after intratumoral injection, and infects cells primarily within the immediate area of the injection tract. Thus, Ad-encoded transgene expression is typically limited to only a small percentage of cells within the tumor.

Assembly of helper-dependent adenovirus DNA into chromatin promotes efficient gene expression.

Helper-dependent adenovirus (hdAd) vectors have shown tremendous potential in animal models of human disease in numerous preclinical studies. Expression of a therapeutic transgene can be maintained for several years after a single administration of the hdAd vector. However, despite the long-term persistence of hdAd DNA in the transduced cell, little is known of the fate and structure of hdAd DNA within the host nucleus.

Rational design of murine secreted alkaline phosphatase for enhanced performance as a reporter gene in mouse gene therapy preclinical studies.

Many preclinical gene therapy studies use a reporter gene to evaluate vector design and performance in mouse models of human disease. Unfortunately, most commonly used reporter genes are immunogenic in mice, which confounds accurate evaluation of vector function. In previous studies, we showed that the murine secreted alkaline phosphatase (mSEAP) gene functions well as a simple and sensitive reporter gene in mice.

Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX.

Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting.