April 29th, 2019 - April 29, 2019 NxGEN Vector Solutions is an Exhibitor at the 22 nd Annual American Society of Gene and Cellular Therapy Meeting.

CEO & Founder, Dr. Susan Faust, meets with ASGCT attendees to discuss NxGEN Vector Solutions’ Transformative Technology at the NxGEN Vector Solutions’ Exhibit Booth in 2019.

January 10th, 2019 - Vandamme et al., 2017, Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial, Human Gene Therapy, Volume 28, No. 11.

“The best trade-off one can currently imagine is to engineer rAAV vectors with better transduction efficiency, carrying optimized therapeutic transgenes and with reduced immunogenic profiles (CpG depleted genome, [Faust et al.], inert capsids, contaminant-free batches, minimum amounts of empty capsids, etc.). Such vectors would provide a higher therapeutic index, as they would permit therapeutic efficiency at doses sufficient to bypass pre-existing humoral immunity, but not high enough to trigger deleterious cellular immunity.”
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October 25th, 2018 - Raikwar et al., 2018, Neuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer’s Disease: Are We There Yet? Journal of Alzheimer’s Disease, Vol. 65.

“It is important to develop suitable strategies to overcome vector directed immune responses. In this regard, CpG-depleted AAV vectors have been shown to evade immune detection [Faust et al.]. In their pioneering studies, Faust et al. initially tested the immunogenicity of AAVrh32.33 in wild type as well as Tlr9 knockout mice. They found that in Tlr9-deficient mice, IFNγ T cell responses toward capsid and transgene antigen were suppressed resulting in minimal cellular infiltrate and stable transgene expression.”
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August 24th, 2018 - Hoffman et al., 2013, Covert Warfare Against the Immune System: Decoy Capsids, Stealth Genomes, and Suppressors, Molecular Therapy, Vol. 21 No. 9.

“Faust et al. hypothesized that a vector genome devoid of CpG motifs would be mostly invisible to TLR9. Sure enough, a vector containing such a stealthy genome packaged into the identical capsid failed to elicit CD8+ T-cell responses to a reporter gene, thus directing long-term expression even in wild-type mice with intact TLR9. The same concept applies to less immunogenic serotypes, where already weak responses can be further reduced. Future studies are likely to adapt this concept to therapeutic gene constructs.”
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June 4th, 2018 - Sebastian et al. 2015, In vivo Gene Correction of Cystic Fibrosis; Cystic Fibrosis in the Light of New Research (Book): Chapter 15, DOI: 5772/60697.

“Strategies aimed at minimizing adaptive immunity to AAV vectors or reducing the need for repeat administration continue within the field. Removing CpG motifs from AAV vectors or designing hybrid AAV capsids has been shown to reduce innate and adaptive immune responses following intramuscular delivery [Faust et al.].”
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May 18th, 2018 - Naso et al., 2017, Adeno-Associated Virus (AAV) as a Vector for Gene Therapy, BioDrugs, 31: 317-314.

“In addition to an adaptive immunological reaction to the capsid of AAV, the transgene can elicit both an adaptive and an innate response…Finally, a transgene with a significant number of CpG dinucleotides can activate innate response through toll-like receptor (TLR) molecular pattern receptors [Faust et al., 2013].”
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March 23rd, 2018 - Mingozzi et al. 2015, Adeno-associated viral vectors at the frontier between tolerance and immunity, Frontiers in Immunology, Vol. (6); Article 120.


“Although both PRRs are part of the same family, recognition of the viral capsid caused induction of a Nuclear Factor kB-dependent inflammatory response (14), while activation of TLR-9 induced secretion of type I interferon (IFN) that was found to be enhanced if vectors with self-complementary (sc) AAV vector genomes were used (15, 16). The nature of this enhanced immunogenicity remains to be clarified, but is maybe related to a negative impact of sc vector genomes on capsid stability (16) or to the additional inverted terminal repeat (ITR) sequence present in sc vector genomes (8). The later hypothesis would be in line with a recent study reporting significantly reduced adaptive immune responses toward the capsid and transgene product when using AAV vectors with a reduced number of CpG motifs, which are known TLR9 PAMP [Faust et al.].”
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