A nucleation-and-growth model for the packaging of genome in linear virus-like particles: impact of multiple packaging signals

Abstract

Inspired by recent experiments on the spontaneous assembly of virus-like particles from a solution containing a synthetic coat protein and double-stranded DNA [Carlos Calcines-Cruz, Ilya J. Finkelstein, and Armando Hernandez-Garcia, Nano Lett. 21 (2021), 2752-2757], we put forward a kinetic model that has as main ingredients a stochastic nucleation and a deterministic growth process. The efficiency and rate of the packaging of the DNA turn out to strongly increase by introducing proteins onto the DNA template that are modified using CRISPR-Cas techniques to bind specifically at predesignated locations, mimicking assembly signals in viruses. Our model shows that treating these proteins as nucleation-inducing diffusion barriers is sufficient to explain experimentally observed increase in encapsulation efficiency, but only if the nucleation rate is sufficiently high. We find an optimum in the encapsulation kinetics for conditions where the number of packaging signals is equal to the number of nucleation events that can occur during time required to fully encapsulate the DNA template, presuming that the nucleation events can only take place adjacent to a packaging signal. Our theory is in satisfactory agreement with the available experimental data.

Biophysical Modeling of SARS-CoV-2 Assembly: Genome Condensation and Budding

“…We recall that the focus of our work is on the regimes in which electrostatics dominates all the other interactions between RNA and N proteins. If, however, the strength of RNA–N protein interaction were weak, the presence of packaging signals or other specific interactions would be necessary to produce a similar genome condensation process [ 62 ]. In that case, each packaging signal would act as a nucleation site for the N proteins to start forming clusters along RNA.…”