Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles

Hofmann, Andreas; Wenzel, Daniela; Becher, Ulrich; Freitag, Daniel F.; Klein, Annette; Eberbeck, Dietmar; Schulte, Maike; Zimmermann, Katrin; Bergemann, Christian; Gleich, Bernhard; Roell, Wilhelm; Weyh, Thomas; Trahms, Lutz; Nickenig, Georg; Fleischmann, Bernd K.; Pfeifer, Alexander

doi:10.1073/pnas.0803746106

Cited by 101 publications

(84 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, we have used in-house synthesized magnetic nanoparticles, 20,29 but magselectofection can be carried out also with commercially available magnetofection reagents (supplemental Figure 1B). 40,41 Similarly, magnetically labeled cells are obtained easily with magnetic nanoparticles that are coated with specific antibodies, which are commercially available for cell separation purposes. 18,19 As an alternative, cells can also be nonspecifically labeled with magnetic nanoparticles as described previously 42,43 (supplemental Figure 7).…”

Section: Discussionmentioning

confidence: 99%

“…Cells manipulated in this manner can be used for a variety of purposes, such as magnetic positioning and magnetically enforced engraftment in target tissues, which is potentially useful in delivering cell-based therapies. [41][42][43] Another important application is tracking of magnetically labeled cells by magnetic resonance imaging. 42,53,54 In conclusion, magselectofection is a versatile integrated procedure for cell sorting and genetic modification.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Sanchez-Antequera

Mykhaylyk

Til

et al. 2011

Blood

View full text Add to dashboard Cite

Research applications and cell therapies involving genetically modified cells require reliable, standardized, and costeffective methods for cell manipulation. We report a novel nanomagnetic method for integrated cell separation and gene delivery. Gene vectors associated with magnetic nanoparticles are used to transfect/transduce target cells while being passaged and separated through a high gradient magnetic field cell separation column. The integrated method yields excellent target cell purity and recovery. Nonviral and lentiviral magselectofection is efficient and highly specific for the target cell population as demonstrated with a K562/Jurkat T-cell mixture. Both mouse and human enriched hematopoietic stem cell pools were effectively transduced by lentiviral magselectofection, which did not affect the hematopoietic progenitor cell number determined by in vitro colony assays. Highly effective reconstitution of T and B lymphocytes was achieved by magselectofected murine wild-type lineage-negative Sca-1 ؉ cells transplanted into Il2rg ؊/؊ mice, stably expressing GFP in erythroid, myeloid, T-, and B-cell lineages. Furthermore, nonviral, lentiviral, and adenoviral magselectofection yielded high transfection/ transduction efficiency in human umbilical cord mesenchymal stem cells and was fully compatible with their differentiation potential. Upscaling to a clinically approved automated cell separation device was feasible. Hence, once optimized, validated, and approved, the method may greatly facilitate the generation of genetically engineered cells for cell therapies. (Blood. 2011;117(16): e171-e181) IntroductionThe feasibility of using genetically engineered cells for therapy in humans has been demonstrated using various cell types, including tumor cells, 1-3 lymphocytes, dendritic cells, 4,5 fibroblasts, 6,7 hematopoietic stem cells (HSCs), 8,9 and mesenchymal stem cells (MSCs). 10,11 Actual or potential applications are as diverse as immune gene therapy for the treatment of cancer, 1-3 cancer therapy with T cells expressing chimeric T-cell receptors, 12,13 the treatment of hereditary diseases, 8,9,[14][15][16] and a plethora of applications in regenerative medicine. 17 With the emerging field of induced pluripotent stem cells, research in genetically engineered cell therapies has reached yet another level of pace and dimension. Clinical applications will require efficient, reliable, standardized methods for cell manipulation. For optimized reproducibility and wide practicality in a decentralized manner, such methods should compose a minimum number of handling steps and be cost-effective and amenable to automation in a closed system.The goal of this work is to provide a novel methodology for performing genetic modification and cell isolation in a single standardized procedure, which we call "magselectofection" ( Figure 1). It integrates nanomagnetic cell separation, which is an approved clinical application, 18,19 and nanomagnetically guided nucleic acid delivery known as magnetofection. [20][21][22] For magneti...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Sanchez-Antequera

Mykhaylyk

Til

et al. 2011

Blood

View full text Add to dashboard Cite

show abstract

“…The use of magnetic forces for site-specific delivery of cells is a relatively new concept that has recently been explored by several groups as a means for improving cell homing efficiency. Notably, the magnetic force in these animal studies was generated using either externally applied permanent magnets (13,65,66) or permanently magnetized nickel-coated stents (10). Targeted delivery of magnetically responsive cells to stented arteries in the presence of a uniform magnetizing field was investigated by our group as a potentially more clinically viable alternative (18).…”

Section: Stent-targeted Cell Delivery Using Mnpmentioning

confidence: 99%

Magnetic nanoparticles for targeted vascular delivery

et al. 2011

View full text Add to dashboard Cite

Magnetic targeting has shown promise to improve the efficacy and safety of different classes of therapeutic agents by enabling their active guidance to the site of disease and minimizing dissemination to nontarget tissues. However, its translation into clinic has proven difficult because of inherent limitations of traditional approaches inapplicable for deep tissue targeting in human subjects and a need for developing well-characterized and fully biocompatible magnetic carrier formulations. A novel magnetic targeting scheme based on the magnetizing effect of deep-penetrating uniform fields is presented as an example of a strategy providing a potentially clinically viable solution for preventing injury-triggered reobstruction of stented blood vessels (in-stent restenosis). The design of optimized magnetic carrier formulations and experimental results showing the feasibility of uniform field-controlled targeting for site-specific vascular delivery of small-molecule pharmaceuticals, biotherapeutics, and cells are discussed in the context of antirestenotic therapy. The versatility of this approach applicable to different classes of therapeutic agents exerting their antirestenotic effects through distinct mechanisms prompts exploring the utility of uniform field-mediated magnetic stent targeting for combination therapies with enhanced efficiencies and improved safety profiles. Additional improvements in terms of site specificity and protracted carrier retention at the site of injury may be expected from the development and use of magnetic carriers exhibiting affinity for arterial wall-specific antigens.

show abstract

“…In contrast, adeno-associated virus vectors are capable of long-term expression, but all known strains lack endothelial tropism in vivo (9). Of note, lentiviral endothelial transfection has recently been accomplished by coupling lentiviral particles to paramagnetic nanoparticles and with subsequent application of magnetic force (10). However, lentiviral-based gene therapy has the capacity to integrate into the host genome at unwanted sites, although the pro-oncogenic potential is less substantial than that in other retroviruses (11).…”

mentioning

confidence: 92%

Nonviral Intercellular Adhesion Molecule-1 Small Interfering Ribonucleic Acid Sequences Transfection In Vivo

Kupatt

2010

Journal of the American College of Cardiology

View full text Add to dashboard Cite

Combined targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles

Abstract: Targeting of viral vectors is a major challenge for in vivo gene

Cited by 101 publications

References 19 publications

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Magselectofection: an integrated method of nanomagnetic separation and genetic modification of target cells

Magnetic nanoparticles for targeted vascular delivery

Nonviral Intercellular Adhesion Molecule-1 Small Interfering Ribonucleic Acid Sequences Transfection In Vivo

Contact Info

Product

Resources

About