With the help of technology advances, target identification and the design/synthesis of their corresponding drugs have become more efficient in recent years than before. However, how to deliver these drugs to hosts is comparably lagging far behind and is the bottleneck step for bringing drugs to benefit patients. Viral vectors, especially adenovirus (AdV) vectors, have been in the center of the research endeavor for delivering genes for the past two decades. However, several considerations about AdV vectors must be appreciated and fully dealt with before their extensive practical application. These issues include those regarding low efficiency for targeted delivery to defined cells or organs, low efficacy due to pre-existing or induced immunity against AdV vectors, and some potential adverse side-effects, such as hepatotoxicity and thrombosis with thrombocytopenia syndrome (TTS), because of off-target sequestration of intravenously administrated AdV vectors. We will fully take advantage of our newly developed method for quickly and efficiently constructing AdV vectors and easily manipulating any part of the AdV genomes to achieve our short-term and long-term goals.

Although two mRNA COVID-19 vaccines played a critical role in the intense campaign against the COVID-19 pandemic, compared to the mRNA platform, AdV vector vaccines have lower costs in production and distribution, don’t need any adjuvants to induce strong immunity, don’t need any extra delivery systems, and don’t have any side effects accompanied with those extra delivery systems. We believe that our delicately engineered AdV vectors will all desirable features and without any severe side effects will have significant impacts on vaccine research and development and will dominate the race against the mRNA platform and other valuable platforms during next pandemic in the near future.

It is known that adeno-associated viruses (AAVs) and lentiviral vectors are currently being used more frequently for in vivo and ex vivo gene delivery, respectively, however, both vectors have their own inherent drawbacks. For example, the major drawback for AAVs is their limited cloning capacity (less than 4.7 kb), which restricts its use in gene delivery of large genes. Moreover, both AAVs and lentiviral vectors could result in insertional mutagenesis in the host genome. Same as for AdV vectors, pre-existing or induced immunity against AAVs also could attenuate the cure effects of AAV-mediate gene therapy. Our AdV vectors, especially gutless AdV vectors, possibly are the only ones that exhibit all of recommended features for a perfect delivery vector, such as absence of random integration, broad tropism, high transduction efficiency, sufficient cargo capacity, evading pre-existing or induced immunity, high safety profiles, etc. These novel AdV vectors could be widely used in the fields of vaccination, virotherapy and gene therapy.