Fig. 7. Scale-up of AAV vector–mediated liver gene transfer of secretable GAA to nonhuman primates. Scale-up of AAV vector–mediated liver gene transfer.

Slides:

Advertisements

Similar presentations

Fig. 1. TP is highly expressed in myeloma.

Advertisements

Fig. 5. Correlation between CD34+CD45RA−CD90+ cell dose, engraftment success, and onset of neutrophil/platelet recovery in nonhuman primates. Correlation.

Fig. 5. Circulating PPi concentration does not correlate with severity of calcification phenotype in mice. Circulating PPi concentration does not correlate.

Fig. 4. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin expression. Intramuscular injection of AAV9-Cas9/sgRNA-51 corrects dystrophin.

BET inhibition and depletion repress the expression of BRCA1 and RAD51

Fig. 6. C3 deficiency resulted in partial sparing of neuron loss in hippocampal CA3 in 16-month-old APP/PS1 mice. C3 deficiency resulted in partial sparing.

Fig. 4. Bexarotene promotes PPARδ activation of target genes in mouse brain and muscle. Bexarotene promotes PPARδ activation of target genes in mouse brain.

Fig. 2. Mechanism of PD-L1 down-regulation in NOD HSPCs.

Fig. 3. Antimicrobial activity is detected in diverse strains of CoNS and not predictable at the species level. Antimicrobial activity is detected in diverse.

β-ARs signal cooperatively with mutant EGFR and inactivate LKB1

Fig. 1. APP/PS1;C3 KO mice show improved cognitive flexibility (reversal) compared to APP/PS1 mice at 16 months of age. APP/PS1;C3 KO mice show improved.

Fig. 1. BCAS1 expression identifies newly generated oligodendrocytes.

Fig. 4. Biomechanical properties of treated tibiae.

Fig. 5. Prophylactic treatment with GS-5734 reduces SARS-CoV disease.

Analysis of brain and spinal cord of treated Gaa−/− mice and controls

Fig. 3. A circadian rhythm in fibroblast wound-healing response.

PVSRIPO-mediated APC activation occurs in immunosuppressive conditions

MRSA virulence proteins cause LMC death and diminished CLV function

Fig. 4. Prion infectivity of skin samples from sCJD patients.

Fig. 3. Serum HBsAg and liver HBV mRNA reduction in chimpanzees dosed with ARC-520. Serum HBsAg and liver HBV mRNA reduction in chimpanzees dosed with.

Fig. 1 MT-2 ameliorates asthmatic pulmonary resistance.

Fig. 6. Increased efficacy of immunotherapy in lymphangiogenic B16 melanomas depends on CCR7 signaling before therapy and local activation and expansion.

Fig. 4 Infection-induced CLV dysfunction is associated with decreased LMC coverage. Infection-induced CLV dysfunction is associated with decreased LMC.

Fig. 5. Pharmacological JAK2 inhibition in vivo abrogates tumor-initiating potential after chemotherapy. Pharmacological JAK2 inhibition in vivo abrogates.

Fig. 3. Fc fusion GDF15 molecules improve metabolic parameters in obese mice and obese cynomolgus monkeys. Fc fusion GDF15 molecules improve metabolic.

Fig. 1. IS mediates a hyperthrombotic uremic phenotype in an AHR-dependent manner across CKD stages. IS mediates a hyperthrombotic uremic phenotype in.

Fig. 3 Biological function of TG2 and the interaction with MT-2.

Fig. 7 Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors. Gel scaffold for inhibition of postsurgical recurrence of B16F10 tumors.

Fig. 5 Combination intravenous reovirus and checkpoint inhibition in an orthotopic syngeneic brain tumor model. Combination intravenous reovirus and checkpoint.

Fig. 4. MATE1 transcription in RCC.

Fig. 6. Safety assessment in cynomolgus monkey.

Fig. 6. Apoptotic MSCs exert in vivo immunosuppression in a TH2-type inflammation model in the absence of cytotoxic cells. Apoptotic MSCs exert in vivo.

Fig. 4. Expression of HGF in liver ECs cooperates with NOX4 inhibition to enhance engraftment of regenerative hepatocytes. Expression of HGF in liver ECs.

Persistence of CAR4 cells is reduced after sustained TCR engagement

Fig. 7. KIF11 informs patient prognosis, and targeting improves survival in a preclinical model. KIF11 informs patient prognosis, and targeting improves.

Fig. 1. mGlu7 expression is reduced in RTT autopsy samples.

Fig. 3. Recovery of AVP-deficient rats from anemia induced by sublethal irradiation. Recovery of AVP-deficient rats from anemia induced by sublethal irradiation.

Fig. 2. STUB1 destabilizes and ubiquitinates TF and mediates TF regulation by AHR. STUB1 destabilizes and ubiquitinates TF and mediates TF regulation by.

Fig. 3. β-AR signaling induces IL-6 in NSCLC cells via activation of PKC and CREB. β-AR signaling induces IL-6 in NSCLC cells via activation of PKC and.

Fig. 5 Local gel scaffold for T cell memory response.

Fig. 2 Fas controls IL-1RA–sEV secretion in murine MSCs.

Fig. 7 Improvement of clinical score and axon pathology by nasal IL-4 treatment during chronic EAE. Improvement of clinical score and axon pathology by.

Molecular Therapy - Methods & Clinical Development

Fig. 1. PGBD5-expressing cells do not tolerate deficiency of nonhomologous end-joining DNA repair. PGBD5-expressing cells do not tolerate deficiency of.

Fig. 5. Nutlin-3 treatment rescues the proliferation and differentiation of NPCs in vitro. Nutlin-3 treatment rescues the proliferation and differentiation.

Comparison of therapeutic efficacies of C12G6 and other bnAbs in mice

Fig. 4 TNF-α up-regulates Fas/Fap-1 expression to promote IL-1RA–sEV release in murine MSCs. TNF-α up-regulates Fas/Fap-1 expression to promote IL-1RA–sEV.

Fig. 3 Chronic work overload leads to mitochondrial calcium overload.

Fig. 3 Tetrode trials and behavioral study in rats.

Fig. 1. β-APP overexpression or exposure to inflammatory mediators induces sIBM-like pathology in cultured rat myocytes that is abrogated by arimoclomol.

Human HFpEF is associated with impaired cardiac myofibril relaxation

Fig. 6 Anticancer effects in PyMT-MMTV syngeneic and MDA-MB-231 xenograft-bearing mice. Anticancer effects in PyMT-MMTV syngeneic and MDA-MB-231 xenograft-bearing.

Fig. 4 Analysis of ISO response in vitro in neonatal cardiomyocytes.

Fig. 5. Prophylactic and therapeutic efficacy of C12G6 in ferrets.

Fig. 4. Local application of FR provides prolonged protection against Gq-dependent airway constriction in normal and OVA-sensitized mice in vivo. Local.

Fig. 2. Cellular response to FolamiRs in vitro.

Fig. 1. Specificity of FolamiR uptake in cancer cells in culture.

Fig. 5 Treatment with an OX40 agonist antibody of 3-week-old HBVtgRag−/− mice or mice with chronic HBV disease results in an altered immune response to.

CSF1 secretion by melanoma cells is induced by CTL-derived cytokines

Fig. 4. Clearance of 12-mer-1 from a nonhuman primate model.

Fig. 2. BET inhibition enhances PARPi-induced DNA damage.

Fig. 6 In utero injection of inflammatory cytokines or adoptive transfer of activated T cells leads to pregnancy loss. In utero injection of inflammatory.

Fig. 1. MSCs undergo in vivo apoptosis after infusion without affecting immunosuppression. MSCs undergo in vivo apoptosis after infusion without affecting.

Fig. 5. Anti-inflammatory effects of silibinin on KA treatment in the hippocampus. (A) Representative coronal sections of the hippocampal CA1 region following.

Western blot of MDA-modified proteins in FVB control, OVE26 diabetic, and catalase-protected OVE26C diabetic hearts. Western blot of MDA-modified proteins.

Neutralization of CSF1 and Ad5-HRG treatment.

Induction of liver NQO1 activity in juvenile female rats treated for 3 d (10 mg/kg qd SERMs or 0.1 mg/kg qd E2 or vehicle control). Induction of liver.

Fig. 7 Heart-specific OMA1 down-regulation protects from hypertrophy induced by TAC. Heart-specific OMA1 down-regulation protects from hypertrophy induced.

Fig. 4 Systemic AAV9 delivery of gene editing components to ΔEx44 mice rescues dystrophin expression. Systemic AAV9 delivery of gene editing components.

Fig. 6 Pharmacologic alterations of β-AR signaling regulate cardiomyocyte abscission and endowment. Pharmacologic alterations of β-AR signaling regulate.

Presentation transcript:

Fig. 7. Scale-up of AAV vector–mediated liver gene transfer of secretable GAA to nonhuman primates. Scale-up of AAV vector–mediated liver gene transfer of secretable GAA to nonhuman primates. (A to C) Male cynomolgus monkeys (n = 3) were treated with AAV8-hAAT-sp7-Δ8-coGAA (AAV-GAA) (2 × 1012 vg/kg) and followed up for 90 days. (A) Western blot analysis of plasma using an anti-GAA antibody. rhGAA was used as loading control. NHP, nonhuman primate. (B) GAA activity in plasma. Basal, endogenous GAA activity in monkeys #1 to #3 before injection and five additional control monkeys (n = 8). Statistical analysis: one-way ANOVA with Tukey’s post hoc. Error bars represent the SD of the mean. (C) GAA activity in liver, heart, diaphragm, biceps, and triceps. Endogenous GAA activity was measured in six monkeys treated with an unrelated AAV vector [control (Ctrl)]. Statistical analysis: multiple t test. Francesco Puzzo et al., Sci Transl Med 2017;9:eaam6375 Published by AAAS