Systematic administration of Adeno-associated virus (AAV) vectors expressing functional genes represents a promising treatment for muscular dystrophy. An AAV-based gene therapy product, Elevidys, has been approved for the treatment of pediatric patients with Duchenne muscular dystrophy. However, very high dose of AAV is required due to its low transduction efficiency in the muscles after intravenous delivery. And high dose of administration could cause severe side effects, especially liver damage. We aimed to engineer novel AAV capsids with enhanced muscle transduction and de-targeting in the liver. By using our AAVarta platform, an AI-aided AAV capsid evolution discovery technology, random peptide insertion capsid libraries based on AAV9 scaffold were generated and screened in non-human primate (NHP). The screening process relies on muscle-specific viral mRNA recovery by using a potent synthetic muscle promoter SCC45. Three weeks after intravenous administration of AAV libraries in the NHP, the muscle and liver tissues were harvested for total RNA isolation, capsid-specific reverse transcription PCR and Next-generation sequencing. The top capsid candidates were selected by AAVarta enrichment ranking analysis and individually produced as recombinant AAVs for validation. By using GFP and firefly luciferase as reporter genes, several variants showed dramatically improved (up to 113 folds) muscle transduction and reduced liver targeting in mice compared to AAV9. One variant AVT919 showed significant improvements in triceps and tibialis anterior over MyoAAV2A, a benchmark myotropic AAV capsid. In Cynomolgus macaque, AVT919 delivered via intravenous injection also demonstrated significantly enhanced transgene expression over AAV9 in the skeletal and cardiac muscles, while the transduction in the liver is comparable to AAV9. To reduce the targeting of AVT919 in the liver, point mutations in different loops were generated and tested in mice. Several variants showed complete liver de-targeting while remained efficient muscle transduction characteristics. To confirm if the liver de-targeting variants can recapitulate the tropism in NHP, a multiplex validation study was conducted. One variant AVT9150 demonstrated efficient muscle transduction and liver de-targeting in NHP. Our engineered myotropic and liver de-targeted AAV capsid would provide efficient and safer delivery platforms for muscle-targeting gene therapy.