nucleofection, and chemical delivery such as lipofection techniques as it has no

impact on cell viability and has high transfection efficiency (Glass et al. 2018).

Currently, nonviral delivery routes for the CRISPR/Cas9 components via the use of

magnetic NPs have the potential to overcome these pitfalls of different techniques

enumerated above. The day is not far when CRISPR/Cas-9 with magnetofection will

revolutionize the field of medical science (Glass et al. 2018; Huth et al. 2004; Berry

et al. 2003).

A proof-of-principle study in an in vitro model showed that stimulating magnetic

NPs with a magnetic field facilitates particle migration across the blood-brain barrier

(Kaushik et al. 2019). After passing the blood-brain barrier, a CRISPR plasmid was

released by an alternate magnetic field trigger.

Magnetofection is an effective approach for primary endothelial cells. Other

applications include advances in ex vivo tissue engineering, designing of tumor

vaccines, targeted therapy for cancer, and cardiovascular therapy. In parallel, an

independent study in a porcine airway model, authors have reported a significant and

rapid improvement in the expression of reporter gene through magnetic NP, which

they attributed to an increase in contact time with the mucociliary cells, thereby

reducing their clearance from the target site (Xenariou et al. 2006).

17.3.1.2 Patient-Derived Xenografts and 3D-Bioprinted Prosthetics

3D-bioprinted organs have huge translational capabilities across in vivo, in vitro, and

ex vivo applications (Ramadan and Zourob 2021). Magnetofection can be a futuris-

tic tool for the successful delivery of 3D-bioprinted scaffold or prosthetics to the

organ before transplantations into the experimental models.

17.3.2 In Vivo Applications

Magnetofection has been widely used for different biological agents (viral and

nonviral vectors, and for the delivery of DNA, nucleic acids, and siRNA) in living

animals. In living animals drug-coated nanoparticles can be injected into systemic

circulation or locally near the disease-affected region. Consequently, magnetic NPs

are attracted and retained in the area of interest in the body by the application of

magnetic field (Fig. 17.4). Magnetofection is a convenient and more effective tool

than electroporation or other chemical methods for the biomolecule delivery to target

cells on different internal organs such as the lungs, kidneys, spleen, GI tract, and

blood vessels. It offers numerous advantages for antisense ODNs (antisense

oligodeoxynucleotides) delivery requiring higher cellular uptake of vector in

minutes and gene expression targeted at the desired site of action. The first report

for the use of in vivo magnetofection was demonstrated by Plank et al. using

magnetic NP complexed with pDNA injected into the pig ear vein (Plank et al.

2003; Scherer et al. 2002). They showed a confined localization of the reporter gene

around the ear vein with magnetic NPs (Scherer et al. 2002). This concept was

further explored in several clinical trials in cats. Currently, the magnetic NPs with

doxorubicin as an anticancer drug are also under clinical trial (Mukherjee et al.

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