All Research Papers Published In Molecular Therapy - Methods & Clinical Development

Research Article
68
10.1016/j.omtm.2020.06.006

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

Jun 10, 2020
Molecular Therapy - Methods & Clinical Development
Yaron Ilan

Research Article
25
10.1016/j.omtm.2020.05.033

Experimental Variables that Affect Human Hepatocyte AAV Transduction in Liver Chimeric Mice

Jun 02, 2020
Molecular Therapy - Methods & Clinical Development
Chenhui Zou + 12 more +12

Research Article
31
10.1016/j.omtm.2020.05.015

Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model

May 22, 2020
Molecular Therapy - Methods & Clinical Development
Kazuki Sawamoto + 6 more +6

Research Article
43
10.1016/j.omtm.2020.04.012

Translational Feasibility of Lumbar Puncture for Intrathecal AAV Administration

Apr 18, 2020
Molecular Therapy - Methods & Clinical Development
Christian Hinderer + 8 more +8

Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distribution in the CSF so that optimal parameters can be replicated in the clinic. In the context of developing a motor neuron-targeted gene therapy for spinal muscular atrophy, we conducted studies in nonhuman primates to evaluate the impact of injection volume on spinal cord transduction after AAV delivery via lumbar puncture. Lumbar injection of an AAVhu68 vector targeted motor neurons throughout the spinal cord, but only in juvenile nonhuman primates administered large injection volumes, equivalent to about half of the total CSF volume. Upon repeating this study with clinically relevant injection volumes and larger animals, we found that lumbar puncture failed to achieve significant transduction of the spinal cord. In contrast, vector administered into the cisterna magna distributed reproducibly throughout the spinal cord in both juvenile and adult animals. These findings highlight the challenges of translating AAV delivery via lumbar puncture to humans and suggest that delivery into the cisterna magna may represent a more feasible alternative.

Research Article
15
10.1016/j.omtm.2020.03.001

Defining the Optimal FVIII Transgene for Placental Cell-Based Gene Therapy to Treat Hemophilia A

Mar 14, 2020
Molecular Therapy - Methods & Clinical Development
Nadia El-Akabawy + 14 more +14

Research Article
34
10.1016/j.omtm.2020.01.006

Factors Impacting Efficacy of AAV-Mediated CRISPR-Based Genome Editing for Treatment of Choroidal Neovascularization

Jan 23, 2020
Molecular Therapy - Methods & Clinical Development
Sook Hyun Chung + 12 more +12

Research Article
30
10.1016/j.omtm.2019.12.020

CAR T Cell Generation by piggyBac Transposition from Linear Doggybone DNA Vectors Requires Transposon DNA-Flanking Regions

Jan 16, 2020
Molecular Therapy - Methods & Clinical Development
David C Bishop + 7 more +7

Research Article
27
10.1016/j.omtm.2019.12.005

ISPD Overexpression Enhances Ribitol-Induced Glycosylation of α-Dystroglycan in Dystrophic FKRP Mutant Mice

Dec 24, 2019
Molecular Therapy - Methods & Clinical Development
Marcela P Cataldi + 4 more +4

Research Article
28
10.1016/j.omtm.2019.12.001

AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains

Dec 10, 2019
Molecular Therapy - Methods & Clinical Development
Michaël Hocquemiller + 16 more +16

Research Article
18
10.1016/j.omtm.2019.11.020

Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease

Dec 06, 2019
Molecular Therapy - Methods & Clinical Development
Sang-Oh Han + 8 more +8