{'fraction_non_alphanumeric': 0.023003194888178913, 'fraction_numerical': 0.014696485623003195, 'mean_word_length': 6.216589861751152, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Chase‐ing regeneration: engineering chondroitinase for mammalian expression

Neurons fail to regenerate following spinal cord injury partly due to the up‐regulation of chondroitin sulfate proteoglycans (CSPGs). Animal models of neuronal injury show enhanced regeneration when treated with chondroitinase, a bacterial enzyme that degrades inhibitory CSPG glycosaminoglycan (GAG) side chains. Unfortunately, this treatment paradigm is limited by the lack of a non‐invasive, sustained delivery method. This study aims to increase the therapeutic potential of chondroitinase by "engineering" the bacterial chondroitinase gene for maximum sustained expression in mammals and by using a lentiviral gene therapy approach for delivery. Injection of "engineered" chondroitinase lentivirus resulted in sustained activity as detected by digestion of GAG chains two weeks post‐injection. Transplantation of primary astrocytes and Schwann cells that were previously transduced with chondroitinase lentivirus also resulted in GAG chain degradation at the two week time point. Lack of macrophage immunoreactivity following both methods of chondroitinase delivery suggests minimal host immune response and supports the non‐invasive nature of our approach. Finally, in contrast to control neurons, preliminary data suggests that chondroitinase transduced neurons extend axons through regions of CSPG in vitro. These data significantly advance the clinical therapeutic potential for chondroitinase. Supported by NIH‐NIDA 1T32 DA022738, NIH‐NINDS 1 P30 NS051220‐01, and KSCHIRT #6‐13.