Synthetic Virus-Derived Nanosystems (SVNs) for Delivery and Precision Docking of Large Multifunctional DNA Circuitry in Mammalian Cells

Abstract

DNA delivery is at the forefront of current research efforts in gene therapy and synthetic biology. Viral vectors have traditionally dominated the field; however, nonviral delivery systems are increasingly gaining traction. Baculoviruses are arthropod-specific viruses that can be easily engineered and repurposed to accommodate and deliver large sequences of exogenous DNA into mammalian cells, tissues, or ultimately organisms. These synthetic virus-derived nanosystems (SVNs) are safe, readily customized, and can be manufactured at scale. By implementing clustered regularly interspaced palindromic repeats (CRISPR) associated protein (CRISPR/Cas) modalities into this system, we developed SVNs capable of inserting complex DNAs into genomes, at base pair precision. We anticipate a major role for SVNs as an attractive alternative to viral vectors in accelerating genome engineering and gene therapy applications in the future.

Solutions against emerging infectious and noninfectious human diseases through the application of baculovirus technologies

“…Nevertheless, a lot of effort is being made to overcome the limitations (Aulicino et al 2020) that other viral vectors used in gene therapy do not escape, where those vectors can generate much greater immune responses as a result of being derived from mammalian pathogens and have other serious disadvantages including the limited duration of the transgenes they carry and the costs of scaled-up production. Thus, several investigations have been reported that have offered improvements in baculoviral vectors for BacMamtype applications.…”

“…In the coming years, owing to the development of more extensive knowledge about baculoviruses, which new perspective will enable the development of the next generation of vectors for producing better-engineered virions that would be more useful for the aforementioned applications and for other innovations, we could expect that these technologies will be well valued by and appropriate for more human-and veterinary-health companies. Furthermore-and in view of the approvals received in recent years by various humangene-therapy products based on viral vectors (Ginn et al 2018) and the new generation of vaccines that use virions (Rawat et al 2021)-we would expect that in this third decade of the twenty-first century, clinical trials in humans may begin to promote BacMam technologies and bring those procedures to the pharmaceutical market (Aulicino et al 2020). The usefulness of the application of baculoviruses in human and animal health is already indisputable.…”

VLP‐factory™ and ADDomer©: Self‐assembling Virus‐Like Particle (VLP) Technologies for Multiple Protein and Peptide Epitope Display

“…Scale bars (50 μm) are drawn in white (adapted from Sari-Ak et al, 2019). genetic code expansion (Koehler et al, 2016), or multifunctional DNA delivery in mammalian and human cells and tissues, among others (Aulicino, Capin, & Berger, 2020;Mansouri et al, 2016;Sari et al, 2016).…”

Nanomedicine & Nanotoxicology Future Could Be Reshaped Post-COVID-19 Pandemic

“…It has also allowed us to realize that what is seen with SARS-CoV-2 is a form of nanotoxicity and that several new tools such as artificial intelligence have been deployed to understand the disease and develop therapies to combat it (Ahuja et al, 2020;Shaker et al, 2020). Therefore, similar tools should be used in the design of future nanotoxicology studies but also in the development of bioinspired drug delivery systems like viruses (Aulicino et al, 2020).…”