• Is willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; a legally authorized representative may provide written consent and assent may be requested.

• Male and female subjects with diagnosis of classic PKU, a condition characterized by severe PAH deficiency with confirmed PAH mutations predicted with no residual enzyme activity. A list of PAH mutations for classic PKU based on in vitro PAH activity (Himmelreich et al., 2018) and the genotype-phenotype correlation (Garbade et al., 2019) can be found in BIOPKU genotypes database (http://www.biopku.org/pah).

• Adults aged 18-55 at the time of informed consent

• Subjects intolerant or unresponsive to available medical therapies, such as Kuvan, Playnzip, etc.

• Subjects who have been on medications, such as Kuvan, Palynziq, etc but have come off for medical reasons or the patient's decision at least 28 days prior to signing the consent form (Subjects who have good disease control on these existing therapies will not be included in this study).

• At least 1 documented measurements of Phe ≥ 600 μmol/L while on usual diet in the preceding 6 months.

• Subjects are willing to record their diet and follow the instruction of dietitians during the trial.

• Willingness and capable per Investigator opinion to comply with study procedures and requirements.

• Women of child bearing potential must be confirmed as negative non pregnant subjects by blood pregnancy test from day -28 to day 0. Subjects must agree to use a highly effective form of contraception from the time of NGGT002 administration until a minimum of 1 year after NGGT002 administration, and for male subjects, a minimum of 3 consecutive semen samples are negative for AAV8 after administration of NGGT002. Highly effective birth control methods include:

‣ documented vasectomy or permanent sterilization

⁃ condom

⁃ combined (estrogen and progestogen-containing) hormonal contraception (oral, intravaginal or transdermal)

⁃ progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)

⁃ intrauterine device

⁃ intrauterine hormone-releasing system

⁃ sexual abstinence is acceptable only as true abstinence and when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, hypothermal, post-ovulation) is not acceptable as a form of abstinence.