Capsid Name	Parental Backbone	Primary Target	Key Improvement	Engineering Method
MyoAAV (4A/4E)	AAV9	Muscle (Global)	10–50x muscle potency; Liver de-targeting; allows massive dose reduction.	Directed Evolution (DELIVER)
AAVMYO	AAV1/6/8/9 Chimer	Muscle / Heart	High specificity for heart and skeletal muscle; superior mRNA expression.	DNA Shuffling + Barcoding
AAV-BI30	AAV9	CNS Vasculature	300x targeting of brain/spinal cord blood vessels; works in human cells.	mRNA-based Evolution
AAV.eM	AAV9/AAV2	Muscle	Global liver de-targeting with high muscle-specific expression in NHPs.	Rational Design / Loop Swap
AAV-PHP.eB	AAV9	CNS (Neurons)	Efficiently crosses the BBB in mice to target neurons and glia.	Directed Evolution
BI-hTFR1	Synthetic	CNS (Human)	Binds Human Transferrin Receptor to cross the human BBB.	Rational / AI Design
AAV-F	AAV9	CNS (NHP)	Efficiently crosses the BBB in multiple species (including Macaques).	Directed Evolution
AAV-LK03	Human Capsids	Liver (Human)	Highly specific for human hepatocytes; evades many pre-existing antibodies.	Shuffling / Human Selection
AAV-DJ	AAV2/8/9 Hybrid	Liver / In Vitro	High efficiency in cell culture and liver targeting in vivo.	DNA Shuffling
7m8	AAV2	Retina	Reaches the outer retina via simple intravitreal (eye) injection.	Directed Evolution
Anc80L65	Ancestral Nodes	Multi-Organ	High efficiency in liver/ear; avoids many pre-existing human antibodies.	Ancestral Reconstruction
AAV.cc47	Synthetic	Kidney	Highly specific for the proximal tubule epithelium in the kidney.	Directed Evolution

Engineering Methodologies

The development of these synthetic capsids generally falls into three categories:

1. Directed Evolution: Creating massive libraries of random variants (billions of versions) and “filtering” them through biological hurdles (e.g., “Which of these billion viruses can reach the brain?”).
2. Rational Design: Using structural biology to make specific “surgical” changes, such as swapping loops or mutating specific surface residues to block liver binding.
3. In Silico / AI Design: Using machine learning and computational modeling (like the Dyno Therapeutics or Apertura platforms) to predict which amino acid sequences will yield better stability or tissue-specific binding.

Common Goals of Synthetic Capsids

• Liver De-targeting: Most natural AAVs get “stuck” in the liver. Engineering aims to reduce this to lower toxicity and increase the “bioavailable” dose for other organs.
• Immune Evasion: Modifying the surface “epitopes” so that the human immune system doesn’t recognize the virus as a threat.
• Dose Reduction: By making the virus more efficient at reaching its target (e.g., the brain), clinicians can use much lower doses, significantly improving patient safety.